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Nonlinear data fitting routines are needed to fit data when a plot of
the data is not a straight line or is not defined by a linear equation. Data fitting routines solve for the values
of the independent variables that best describe the dependent data. For
example the intravenous bolus dose pharmacokinetic equation for a one
compartment open model predicts the state state concentrations post
dose, Cp=Salt*Fraction*Dose*exp(-K*Time Post Dose) / (Vd*(1-exp(-K*Dosage
Interval)). The known variables are dose, salt of the drug, fraction
absorbed is assumed to be 1 for IV doses, time of post dose level(s), level(s)
at the time(s), and dosage interval. The independent pharmacokinetic variables to be
determined are Vd (volume of distribution) and Cl (clearance).
Note K (elimination rate
constant) = Cl / Vd. The dependent data are the concentrations (Cp).
The function to minimize during data fitting is the Sum of the Square of the Errors = Sum for
all levels (Predicted Level - Actual Level)^2 or a
weighted or Bayesian version of this equation. During
the SSE minimization process the predicted and actual levels approach each other as
changes in the values of the independent parameters are made
until the parameters that the minimum SSE are found. The independent
parameters that minimize the SSE can then be used for dosage adjustments and
serum level predictions.
The complete iterative data fitting process consist of an
equation(s) to predict levels using the independent parameters and know
variables, calculation of the SSE, convergence criteria, and a data fitting algorithm that
determines the independent parameters that minimizes the SSE.
There
are numerous nonlinear fitting methods such as Simplex, Gauss-Newton,
damping Gauss-Newton, and modified Marquardt. Algorithms for the data
fitting methods in PHP programming language will be provide. The
mathematical theory of the methods will not be discussed, but a practical
approach to using them will be provided.
Simplex Nonlinear
Data Fitting MethodThe Simplex routine is used in chemical
engineering and doesn't require a "good" initial estimate of the independent
variables to find a solution that minimizes the SSE. It also doesn't require the
derivate of the prediction equation to be calculated . The Simplex
algorithm's interworkings are quite complex and flow charting of the
algorithm is suggested for a more thorough understanding. A simplified
explanation is provided below and comments are included in the PHP code for
the Simplex algorithm.
A function in PHP is required to calculated the SSE. This function calls the
level function that calculates the predicted levels using the most recent
independent parameters calculated by the Simplex routine. The SSE function
loops through the know levels, to
calculate their respective predicted levels using the most recent estimate
of the indepent parameters and the known variables in an appropriate equation for the
data being fit. The results of the calculated levels are supplied to the SSE
function which calculates the SSE for all known levels and
their respective predicted values. Convergence criteria are checked and if
convergence is acheived the Simplex routine returns the current independent parameters
and exits the Simplex function, if not further processing continues in the
Simplex routine with new independent parameter estimates repeating the cycle until convergence
is acheived.
Sum of Square of
Errors (SSE) = Sum
for all levels (Predicted Level - Actual Level)^2
Predicted Level
(mg/L) =Salt*Fraction*Dose
(mg)*exp(-K
(1/hours)*Time
Post Dose
(Hours) / (Vd
(liters)*(1-exp(-K
(1/hours)*Dosage
Interval
(hours)))
Storing the know
variables in arrays is recommended as they can then be used within loops and
varibles can be identified by the loop index, for example
Predicted
Level =Salt*Fraction*Dose*exp(-K*TimePostDose(I))/
(Vd*(1-exp(-K*DosageInterval))
As this is a steady state equation for
a set dosing regimen the dose, salt, and fraction, and dosage interval are
uniform and unchanging and may not require an index.
This is a very simple example, but if you are writing code for non-steady
state data with changing doses and frequences then all of the know varibles
could be indexed for easy retrival.
Pseudo code for SSE calculation
SSE =0
For I= 1
to Number of Levels
Predicted Level
=Salt*Fraction*Dose*exp(-K*TimePostDose(I))/ (Vd*(1-exp(-K*DosageInterval))
SSE = SSE + (Predicted
Level - Actual Level(I) )^2
Next I
The
following PHP code is the Simplex Fitting Routine
The user will need
to supply a function to calculated the sum of square of errors and a
function to calculates the predicted levels.
<?php
/**
* Simplex
*
* This function implements a Nelder-Mead Simplex
optimization algorithm to fit pharmacokinetic parameters
* (Volume of
Distribution and/or Clearance) by minimizing the sum of squared errors
(SSE). It iteratively
* adjusts parameter estimates to find the optimal
values that best fit the provided data. The function supports
* fitting
either both Volume of Distribution (Vd) and Clearance (Cl) or only
Clearance, depending on the setting of the
* $FitVdCL flag (Yes, No). This can be set
depending on the type of level data you have. If only trough levels were
collected without peaks only clearance should be determined
* and Vd will be
set at the population mean value by setting the flag to "No". If the flag is set to Yes both Vd and Clearance will be determined.
*
* @global array
$EliminationRatePop Population elimination rate
* @global float $VdPop
Population volume of distribution
* @global array $NL, $CY, $TX, $TC,
$IB, $OD, $II, $IR, $TD, $ND, $CZ, $TS, $KA Input data arrays for SSE
calculation
* @global float $SumofSquareofErrors Stores the final SSE
value
* @global float $EliminationRateFit Fitted elimination rate
*
@global float $VdFit Fitted volume of distribution
* @global float
$ClearanceFit Fitted clearance
* @global array $P, $PP, $PF Arrays for
parameter storage
* @global int $M Number of independent variables to fit
* @global string $FitVdCL Flag indicating whether to fit both Vd and Cl
("Yes") or only Cl ("No")
* @global array $FitScr, $TSCRR, $SCR, $Drug,
$CreatinineClearance, $LeanBodyWeight, $Age, $Height, $Weight, $Sex, $BSA,
$TimeStartingLevel Additional input parameters
*
* @return array $P
Array containing the optimized parameter estimates (Vd and/or Cl)
*/
function Simplex() {
// Global variables used in the function. These will have to be adjusted with the varibles required by you
sum of the square equation, level prediction function, and other varibles required
by your code.
// The bolded variables should not be changed unless you replace
their names in the Simplex routine.
global
$EliminationRatePop, $VdPop, $NL, $CY, $TX, $TC, $IB,
$OD, $II, $IR, $TD, $ND, $CZ, $TS, $KA,
$SumofSquareofErrors;global
$EliminationRateFit, $VdFit, $ClearanceFit, $P, $PP, $PF,
$M,
$FitVdCL,
$FitScr, $SCR, $Drug, $CreatinineClearance, $LeanBodyWeight, $Age, $Height,
$Weight, $Sex, $BSA, $TimeStartingLevel, $TSCRR;
// Initialize arrays
for Simplex algorithm.
Do not change these names.$A = array_fill(0, 6, array_fill(0, 6, 0)); //
Matrix A: A[0][j] stores SSE for parameter pairs; A[1][j] and A[2][j] store
Vd and Cl estimates
$X = array_fill(0, 6, array_fill(0, 6, 0)); // Matrix
X: Used for calculating centroid and other intermediate points
$P =
array_fill(0, 3, 0); // Current parameter estimates (Vd and/or Cl)
$PP =
array_fill(0, 3, 0); // Stores population parameter values
// Simplex
algorithm constants.
Do not change these names.$AA = 1; // Reflection coefficient
$BB = 0.5; //
Contraction coefficient
$CC = 2; // Expansion coefficient
$SG = 1 *
(10**10); // Previous sum of SSE for convergence check
$PC = 0.00001; //
Convergence threshold
$M = 2; // Number of independent variables in the
prediction equation which are (Vd and Cl by default) in this example and can
be overidden by the $FitVdCL Flag in code below. The value of $M may be
changed for you prediction equation.
$SS = 0; // Current sum of squared errors
$SR = 0; //
Sum of SSE for current iteration
$CK = 0; // Sum of SSE for convergence
check
$J = 0; // Loop counter
$JS = 0; // Index of second-highest SSE
$JH = 0; // Index of highest SSE
$JL = 0; // Index of lowest SSE
$SRold = 0; // Previous SR value (not used in current code).
This can be removed.
//
Initialize population parameters. These are your inital estimates of the
values of the independent parameters for the patient based on population
mean values.
$A[1][1] = $VdPop; // A[1][1]:
Population Volume of Distribution
$A[2][1] = ($VdPop *
$EliminationRatePop); // A[2][1]: Population Clearance (Cl = Vd *
Elimination Rate)
// Handle case where only Clearance is fitted
if
($FitVdCL == "No") {
$M = 1; // Set to fit only one parameter (Clearance)
$A[1][1] = $A[2][1]; // Set A[1][1] to Clearance for single-parameter
fitting
}
// Copy population parameters to PP array
for ($I =
1; $I <= $M; $I++) {
$PP[$I] = $A[$I][1]; // Store population Vd (PP[1])
and/or Cl (PP[2])
}
// Generate initial simplex vertices (M+1
parameter sets, including population estimates)
//
randomized parameter pairs
// A(1,1) population Vd
A(1,2) A(1,3)
// A(2,1) population Cl
A(2,2) A(2,3)
//
for ($J = 2; $J <= $M +
1; $J++) {
for ($I = 1; $I <= $M; $I++) {
do {
// Randomize
parameter estimates around population mean values for the patient
$A[$I][$J] = abs(2 * rand(0,
1) * $A[$I][1] + 0.01 * (rand(0, 1) - 0.5));
} while ($A[$I][$J] == 0);
// Ensure non-zero parameters
}
}
// Evaluate initial SSE for
each vertex
for ($K = 1; $K <= $M + 1; $K++) {
for ($I = 1; $I <= $M;
$I++) {
$P[$I] = $A[$I][$K]; // Set current independent parameters for SSE
calculation
}
// Set fitted parameters based on fitting mode
if
($FitVdCL == "Yes") {
$ClearanceFit = $P[2]; // Clearance
$EliminationRateFit = $P[2] / $P[1]; // Elimination rate = Cl / Vd
$VdFit
= $P[1]; // Volume of Distribution
} else {
$ClearanceFit = $P[1]; //
Clearance only
$EliminationRateFit = $ClearanceFit / $VdPop;
$VdFit =
$VdPop;
}
// Calculate SSE using external function SS(). Replace
this function with your own throughout the code.
$SS =
SS($NL, $CY, $TX, $TC, $IB, $OD, $II, $IR, $TD, $P, $ND, $CZ, $TS, $KA, $PP,
$PF, $VdPop, $FitVdCL, $FitScr, $TSCRR, $SCR, $Drug, $EliminationRatePop,
$CreatinineClearance, $LeanBodyWeight, $Age, $Sex, $Height, $BSA,
$TimeStartingLevel);
$A[0][$K] = $SS; // Store SSE for current parameter
set
// print "SS = " . $SS . "<br>"; // Debugging: Comment out in
production
}
// Main Simplex optimization loop
while (true) {
// Calculate sum of SSEs for convergence check
$SR = 0;
for ($I = 1;
$I <= $M + 1; $I++) {
$SR += $A[0][$I]; // Sum of SSEs for all vertices
}
$CK = 0;
for ($K = 1; $K <= $M + 1; $K++) {
$CK += $A[0][$K]; //
Duplicate sum for convergence check
}
//
Check for convergence
if ($CK < 0.001 || (abs($SR - $SG) <= $PC * $SG)) {
for ($I = 1; $I <=
$M; $I++) {
$P[$I] = $A[$I][$JL]; // Set final parameters to those with
lowest SSE
}
if ($FitVdCL == "Yes") {
$ClearanceFit = $P[2];
$EliminationRateFit = $P[2] / $P[1];
$VdFit = $P[1];
} else {
$ClearanceFit = $P[1];
$EliminationRateFit = $ClearanceFit / $VdPop;
$VdFit = $VdPop;
}
$SumofSquareofErrors = $A[0][$JL]; // Store final
SSE
return $P; // Return optimized parameters
}
// Update
previous SSE sum for next iteration
if (abs($SR - $SG) > $PC * $SG) {
$SG = $SR;
}
// Identify highest and lowest SSE indices
$SR =
0;
$SL = 1 * 10**10;
for ($J = 1; $J <= $M + 1; $J++) {
if ($SR <
$A[0][$J]) {
$JH = $J; // Index of highest SSE
$SR = $A[0][$J];
}
if ($SL > $A[0][$J]) {
$JL = $J; // Index of lowest SSE
$SL =
$A[0][$J];
}
}
// Identify second-highest SSE
$SR = 0;
for ($J = 1; $J <= $M + 1; $J++) {
if ($J != $JH && $SR < $A[0][$J]) {
$JS = $J; // Index of second-highest SSE
$SR = $A[0][$J];
}
}
// Calculate centroid of parameters (excluding worst vertex)
for ($I
= 1; $I <= $M; $I++) {
$X[0][$I] = 0;
for ($J = 1; $J <= $M + 1; $J++)
{
if ($J != $JH) {
$X[0][$I] += $A[$I][$J]; // Sum parameters
excluding highest SSE
}
}
$X[0][$I] /= $M; // Average to get
centroid
}
// Reflection: Compute new point by reflecting worst
vertex over centroid
for ($I = 1; $I <= $M; $I++) {
do {
$A[$I][0]
= abs((1 + $AA) * $X[0][$I] - $AA * $A[$I][$JH]); // Reflection formula
$P[$I] = $A[$I][0];
} while ($A[$I][0] == 0); // Ensure non-zero
parameters
}
// Update fitted parameters
if ($FitVdCL == "Yes")
{
$ClearanceFit = $P[2];
$EliminationRateFit = $P[2] / $P[1];
$VdFit = $P[1];
} else {
$ClearanceFit = $P[1];
$EliminationRateFit
= $ClearanceFit / $VdPop;
$VdFit = $VdPop;
}
// Calculate SSE
for reflected point
$SS = SS($NL, $CY, $TX, $TC, $IB, $OD, $II, $IR, $TD,
$P, $ND, $CZ, $TS, $KA, $PP, $PF, $VdPop, $FitVdCL, $FitScr, $TSCRR, $SCR,
$Drug, $EliminationRatePop, $CreatinineClearance, $LeanBodyWeight, $Age,
$Sex, $Height, $BSA, $TimeStartingLevel);
$SR = $SS;
//
Code Branches
based on reflected SSEif ($SR <= $A[0][$JS]) { // Reflected SSE is
better than or equal to second-highest
if ($SR < $A[0][$JL]) { //
Reflected SSE is better than lowest
// Expansion: Try a point further in
the direction of reflection
for ($I = 1; $I <= $M; $I++) {
$X[1][$I] =
abs($CC * $A[$I][0] + (1 - $CC) * $X[0][$I]);
$P[$I] = $X[1][$I];
}
if ($FitVdCL == "Yes") {
$ClearanceFit = $P[2];
$EliminationRateFit =
$P[2] / $P[1];
$VdFit = $P[1];
} else {
$ClearanceFit = $P[1];
$EliminationRateFit = $ClearanceFit / $VdPop;
$VdFit = $VdPop;
}
// Calculate SSE for expanded point
$SS = SS($NL, $CY, $TX, $TC, $IB,
$OD, $II, $IR, $TD, $P, $ND, $CZ, $TS, $KA, $PP, $PF, $VdPop, $FitVdCL,
$FitScr, $TSCRR, $SCR, $Drug, $EliminationRatePop, $CreatinineClearance,
$LeanBodyWeight, $Age, $Sex, $Height, $BSA, $TimeStartingLevel);
$SL =
$SS;
if ($SL < $SR) { // Expanded point is better
for ($I = 1; $I
<= $M; $I++) {
$A[$I][$JH] = $X[1][$I]; // Replace worst vertex with
expanded point
}
$A[0][$JH] = $SL;
continue; // Check convergence
}
}
// Reflected point is acceptable (better than second-highest but
not lowest)
for ($I = 1; $I <= $M; $I++) {
$A[$I][$JH] = $A[$I][0]; //
Replace worst vertex with reflected point
}
$A[0][$JH] = $SR;
continue; // Check convergence
} //
end of code branch// Reflected SSE is between
second-highest and highest
if ($SR < $A[0][$JH]) {
for ($I = 1; $I <=
$M; $I++) {
$A[$I][$JH] = $A[$I][0]; // Replace worst vertex with
reflected point
}
$A[0][$JH] = $SR;
}
// Contraction: Try a
point closer to centroid
for ($I = 1; $I <= $M; $I++) {
$A[$I][0] =
abs($BB * $A[$I][$JH] + (1 - $BB) * $X[0][$I]); // Contraction formula
$P[$I] = $A[$I][0];
}
if ($FitVdCL == "Yes") {
$ClearanceFit =
$P[2];
$EliminationRateFit = $P[2] / $P[1];
$VdFit = $P[1];
} else
{
$ClearanceFit = $P[1];
$EliminationRateFit = $ClearanceFit / $VdPop;
$VdFit = $VdPop;
}
// Calculate SSE for contracted point
$SS =
SS($NL, $CY, $TX, $TC, $IB, $OD, $II, $IR, $TD, $P, $ND, $CZ, $TS, $KA, $PP,
$PF, $VdPop, $FitVdCL, $FitScr, $TSCRR, $SCR, $Drug, $EliminationRatePop,
$CreatinineClearance, $LeanBodyWeight, $Age, $Sex, $Height, $BSA,
$TimeStartingLevel);
$SR = $SS;
if ($SR < $A[0][$JH]) { //
Contracted point is better than worst
for ($I = 1; $I <= $M; $I++) {
$A[$I][$JH] = $A[$I][0]; // Replace worst vertex
}
$A[0][$JH] = $SR;
continue; // Check convergence
}
// Reduction: Shrink simplex
towards best vertex
for ($K = 1; $K <= $M + 1; $K++) {
for ($I = 1; $I
<= $M; $I++) {
$A[$I][$K] = abs(($A[$I][$K] + $A[$I][$JL]) / 2); //
Average with best vertex
$P[$I] = $A[$I][$K];
}
if ($FitVdCL ==
"Yes") {
$ClearanceFit = $P[2];
$EliminationRateFit = $P[2] / $P[1];
$VdFit = $P[1];
} else {
$ClearanceFit = $P[1];
$EliminationRateFit
= $ClearanceFit / $VdPop;
$VdFit = $VdPop;
}
// Calculate SSE
for new vertex
$SS = SS($NL, $CY, $TX, $TC, $IB, $OD, $II, $IR, $TD, $P,
$ND, $CZ, $TS, $KA, $PP, $PF, $VdPop, $FitVdCL, $FitScr, $TSCRR, $SCR,
$Drug, $EliminationRatePop, $CreatinineClearance, $LeanBodyWeight, $Age,
$Sex, $Height, $BSA, $TimeStartingLevel);
$A[0][$K] = $SS;
}
continue; // Check convergence
}
}
?> //end of
Simplex routine
Even though the
Simplex routine is roboust it sometimes coverges on a local minimum which is not
the best SSE solution. In testing this occurs in about 1 out of 5 runs.
The following code can be use to select the independent parameters with the
lowest SSE in 5 consecutive runs of the Simples algorithm.
for ($i=1; $i<=5; $i++){
Simplex();
For ($j=1;$j<=$M;$j++){
$XX[$j][$i]=$P[$j];
$SSS[$i]=$SumofSquareofErrors; //sum of squares for each parameter
}
}
$SSL=1E10;
for ($i=1;$i<=5;$i++){
if ($SSL>$SSS[$i]){
$SSL=$SSS[$i];
$Low=$i; //pointer or index of lowest sum of squares
}
}
for ($i=1;$i<=$M;$i++){
$P[$i]=$XX[$i][$Low];
}
if ($M==1) {
$ClearanceFit=$P[1];
$VdFit=$VdPop;
$EliminationRateFit=$ClearanceFit/$VdFit;
} else {//$M=2
$VdFit=$P[1];
$ClearanceFit=$P[2];
$EliminationRateFit=$P[2]/$P[1];
}
$SumofSquareofErrors=$SSL;
The following is the ouptput while running the Simplex routine using the
above code with print statements embedded in the Simplex routine. Vd and Cl
were determined. P(1) is Vd, P(2)
is clearance, and SS is sum of the square of errors. The patient input data was
age 73, height 70 inches, weight 83 kg, male, serum creatinine 1.3 mg/dL,
and vancomycin 1500 mg over 2 hours every 24 hours. Initial estimated levels
were a peak 36.54 mcg/ml, trough 11.31 mcg/ml, and AUC 521.6 based on mean
population parameters for the patient. Actual steady state serum
levels analyzed were peak 46 mcg/ml and trough 20 mcg/ml, using a
Bayesian SSE method. The initial population mean parameter estimates for the patient were Vd
53.95 Liters and clearance 2.875535 L/Hr. Finally estimates for each run can be seen
below with a Vd of ~ 53 Liters and clearance of 2.08 L/Hr. The Bayesian estimated levels were peak 44.54
mcg/m, trough of 18.84 mcg/ml, and AUC of
720.8.
First run.
Line 936, P(1), 53.95,Line 936, P(2), 2.875535,SS,
9.3643499409975,
Line 936, P(1), 107.905,Line 936, P(2), 5.75607,SS,
59.622407046901,
Line 936, P(1), 107.895,Line 936, P(2), 0.005,SS,
77.165687432929,
Line 1145, P(1), 53.96,Line 1145, P(2), 8.626605,SS,
136.49702633951,
Line 1205, P(1), 94.41125,Line 1205, P(2),
2.16040125,SS, 13.548704764998,
Line 1145, P(1), 40.45625,Line 1145,
P(2), 0.72013375,SS, 91.254183988824,
Line 1205, P(1), 91.0428125,Line
1205, P(2), 4.1370190625,SS, 28.163525800076,
Line 1145, P(1),
57.3184375,Line 1145, P(2), 0.8989171875,SS, 42.041227874484,
Line 1205,
P(1), 82.61171875,Line 1205, P(2), 3.32749359375,SS, 14.980512154019,
Line 1145, P(1), 65.74953125,Line 1145, P(2), 1.70844265625,SS,
6.5070395587565,
Line 1328, P(1), 57.3184375,Line 1328, P(2),
0.8989171875,SS, 42.041227874484,
Line 1145, P(1), 25.28828125,Line 1145,
P(2), 2.42357640625,SS, 60.900311260149,
Line 1205, P(1),
77.1305078125,Line 1205, P(2), 2.2261950390625,SS, 6.035364357943,
Line
1145, P(1), 88.9300390625,Line 1145, P(2), 1.0591026953125,SS,
29.477443590174,
Line 1205, P(1), 62.695009765625,Line 1205, P(2),
2.4214269238281,SS, 2.7144792350349,
Line 1145, P(1),
74.075986328125,Line 1145, P(2), 2.9391793066406,SS, 8.8793626915438,
Line 1205, P(1), 67.831145019531,Line 1205, P(2), 2.0161268188477,SS,
3.7285238280642,
Line 1145, P(1), 53.395646972656,Line 1145, P(2),
2.2113587036133,SS, 1.2278288115913,
Line 1328, P(1),
41.528216552734,Line 1328, P(2), 2.2039405358887,SS, 5.7611958715566,
Line 1145, P(1), 48.25951171875,Line 1145, P(2), 2.6166588085937,SS,
7.4770444616689,
Line 1205, P(1), 62.938236694336,Line 1205, P(2),
2.1662598162842,SS, 2.0086012281893,
Line 1145, P(1),
53.638873901367,Line 1145, P(2), 1.9561915960693,SS, 1.2691280078096,
Line 1145, P(1), 44.096284179688,Line 1145, P(2), 2.0012904833984,SS,
2.5586453757923,
Line 1205, P(1), 58.227748565674,Line 1205, P(2),
2.1250174830627,SS, 1.2523905821479,
Line 1145, P(1),
57.984521636963,Line 1145, P(2), 2.3801845906067,SS, 2.1242754543543,
Line 1205, P(1), 54.725285835266,Line 1205, P(2), 2.0621898447037,SS,
0.98978939820965,
Line 1145, P(1), 49.893184242249,Line 1145, P(2),
2.1485310652542,SS, 1.3423933053167,
Line 1205, P(1),
56.144107484818,Line 1205, P(2), 2.1308958786106,SS, 1.0524844598431,
Line 1145, P(1), 57.473746347427,Line 1145, P(2), 1.981727019701,SS,
1.5445676715039,
Line 1205, P(1), 54.415171816349,Line 1205, P(2),
2.1539507826352,SS, 1.0160141910302,
Line 1145, P(1),
52.996350166798,Line 1145, P(2), 2.0852447487283,SS, 0.93598595239744,
Line 1328, P(1), 51.422471507788,Line 1328, P(2), 2.0624191837871,SS,
0.98312308160617,
Line 1145, P(1), 53.306464185715,Line 1145, P(2),
1.9934838107967,SS, 1.08873271303,
Line 1205, P(1), 54.13799490869,Line
1205, P(2), 2.1138340396756,SS, 0.95502259747468,
Line 1145, P(1),
52.409059240222,Line 1145, P(2), 2.1368889437002,SS, 1.0244297563951,
Line 1205, P(1), 54.146229186505,Line 1205, P(2), 2.0808646194528,SS,
0.94871203467381,
Line 1145, P(1), 53.004584444612,Line 1145, P(2),
2.0522753285055,SS, 0.94857658242955,
Line 1145, P(1),
51.854705424905,Line 1145, P(2), 2.056655457781,SS, 0.96349277904069,
Line 1205, P(1), 53.573348246105,Line 1205, P(2), 2.0748123290348,SS,
0.93831286408523,
Line 1145, P(1), 53.56511396829,Line 1145, P(2),
2.1077817492576,SS, 0.94554370406359,
Line 1205, P(1),
53.424981587371,Line 1205, P(2), 2.0939051440696,SS, 0.93702125843001,
Line 1145, P(1), 52.847983508064,Line 1145, P(2), 2.104337563763,SS,
0.9507009481261,
Line 1205, P(1), 53.392007061595,Line 1205, P(2),
2.0821936377169,SS, 0.93489089231525,
Line 1145, P(1),
52.963375641021,Line 1145, P(2), 2.0735332423756,SS, 0.93580499817057,
Line 1145, P(1), 53.359032535818,Line 1145, P(2), 2.0704821313642,SS,
0.9376268126647,
Line 1205, P(1), 53.087020759053,Line 1205, P(2),
2.0815540943873,SS, 0.93475708051412,
Line 1145, P(1),
53.515652179626,Line 1145, P(2), 2.0902144897286,SS, 0.93626423301793,
Line 1205, P(1), 53.101444775673,Line 1205, P(2), 2.0777035542138,SS,
0.93472796921555,
Line 1145, P(1), 52.796458473131,Line 1145, P(2),
2.0770640108842,SS, 0.93703439456379,
Line 1205, P(1),
53.243119914479,Line 1205, P(2), 2.0809112310087,SS, 0.93445768689534,
Line 1145, P(1), 53.257543931098,Line 1145, P(2), 2.0770606908353,SS,
0.93486863776831,
Line 1205, P(1), 53.129651552064,Line 1205, P(2),
2.0804307434993,SS, 0.93455705340509,
Line 1145, P(1),
53.27132669087,Line 1145, P(2), 2.0836384202942,SS, 0.93454243410312,
Line 1145, P(1), 53.384795053285,Line 1145, P(2), 2.0841189078036,SS,
0.93485204945782,
Line 1205, P(1), 53.193437427369,Line 1205, P(2),
2.0813527845753,SS, 0.93445465844876,
Line 1145, P(1),
53.165230650978,Line 1145, P(2), 2.0786255952899,SS, 0.93455763943743,
Line 1205, P(1), 53.244802680897,Line 1205, P(2), 2.0823852140431,SS,
0.93446558869695,
Line 1145, P(1), 53.191754660951,Line 1145, P(2),
2.079878801541,SS, 0.93447304032999,
Line 1205, P(1),
53.231540675911,Line 1205, P(2), 2.0817586109176,SS, 0.93444728053971,
Line 998, P(1), 53.193437427369,Line 998, P(2), 2.0813527845753,SS,
0.93445465844876,
Second run.
Line 936, P(1), 53.95,Line 936,
P(2), 2.875535,SS, 9.3643499409975,
Line 936, P(1), 0.005,Line 936, P(2),
0.005,SS, 794447644.86191,
Line 936, P(1), 107.905,Line 936, P(2),
5.75607,SS, 59.622407046901,
Line 1145, P(1), 161.85,Line 1145, P(2),
8.626605,SS, 141.10949498637,
Line 1205, P(1), 121.38875,Line 1205, P(2),
6.47120375,SS, 76.71154722612,
Line 1145, P(1), 40.46625,Line 1145, P(2),
2.16040125,SS, 6.1830089200783,
Line 1328, P(1), 0.0049999999999955,Line
1328, P(2), 0.0050000000000008,SS, 794447644.86219,
Line 1145, P(1),
13.48875,Line 1145, P(2), 0.72013375,SS, 382.96217959187,
Line 1205,
P(1), 77.5565625,Line 1205, P(2), 4.1370190625,SS, 27.684433459691,
Line
1145, P(1), 16.8596875,Line 1145, P(2), 0.8989171875,SS, 196.47697442329,
Line 1205, P(1), 62.38234375,Line 1205, P(2), 3.32749359375,SS,
15.019982715254,
Line 1145, P(1), 32.03390625,Line 1145, P(2),
1.70844265625,SS, 15.66561310274,
Line 1205, P(1), 54.795234375,Line
1205, P(2), 2.922730859375,SS, 9.8941981932495,
Line 1145, P(1),
39.621015625,Line 1145, P(2), 2.113205390625,SS, 6.4596102928092,
Line
1145, P(1), 26.137265625,Line 1145, P(2), 1.398071640625,SS, 39.56608348031,
Line 1205, P(1), 46.99681640625,Line 1205, P(2), 2.5061691601563,SS,
6.322996897942,
Line 1145, P(1), 47.84205078125,Line 1145, P(2),
2.5533650195312,SS, 6.6152954518458,
Line 1205, P(1),
41.676274414063,Line 1205, P(2), 2.2232452978516,SS, 5.8875557452856,
Line 1145, P(1), 35.145708007813,Line 1145, P(2), 1.8774773876953,SS,
10.121037576455,
Line 1205, P(1), 44.034039306641,Line 1205, P(2),
2.348996217041,SS, 5.8002618597171,
Line 1145, P(1), 45.244063720703,Line
1145, P(2), 2.4118402648926,SS, 5.9175003663755,
Line 1205, P(1),
44.049610290527,Line 1205, P(2), 2.3489805111694,SS, 5.7884816626377,
Line 1145, P(1), 46.407375183105,Line 1145, P(2), 2.4747314303589,SS,
6.1690014923607,
Line 1205, P(1), 42.859049606323,Line 1205, P(2),
2.2861168309784,SS, 5.7739024550989,
Line 1145, P(1), 42.87462059021,Line
1145, P(2), 2.2861011251068,SS, 5.7611474167107,
Line 1328, P(1),
42.294911231995,Line 1328, P(2), 2.2546535791397,SS, 5.7894788372901,
Line 1145, P(1), 41.684059906006,Line 1145, P(2), 2.2232374449158,SS,
5.8806154439256,
Line 1205, P(1), 43.458222694397,Line 1205, P(2),
2.317544744606,SS, 5.7624286969719,
Line 1145, P(1), 43.473793678284,Line
1145, P(2), 2.3175290387344,SS, 5.7501950017264,
Line 1328, P(1),
43.781165714264,Line 1328, P(2), 2.3332351426125,SS, 5.7507311731608,
Line 1145, P(1), 42.890191574097,Line 1145, P(2), 2.2860854192352,SS,
5.7484190835192,
Line 1328, P(1), 42.606176013947,Line 1328, P(2),
2.2703557565498,SS, 5.7532350987657,
Line 1145, P(1), 43.48936466217,Line
1145, P(2), 2.3175133328629,SS, 5.7379867683543,
Line 1328, P(1),
43.796736698151,Line 1328, P(2), 2.3332194367409,SS, 5.7387835376217,
Line 1145, P(1), 42.905762557983,Line 1145, P(2), 2.2860697133636,SS,
5.7357174127517,
Line 1328, P(1), 42.621746997833,Line 1328, P(2),
2.2703400506783,SS, 5.7402887598184,
Line 1145, P(1),
43.504935646057,Line 1145, P(2), 2.3174976269913,SS, 5.7258039568797,
Line 1328, P(1), 43.812307682037,Line 1328, P(2), 2.3332037308693,SS,
5.7268607156551,
Line 1145, P(1), 42.92133354187,Line 1145, P(2),
2.2860540074921,SS, 5.7230423617136,
Line 1328, P(1), 42.63731798172,Line
1328, P(2), 2.2703243448067,SS, 5.72736964833,
Line 1145, P(1),
43.520506629944,Line 1145, P(2), 2.3174819211197,SS, 5.7136465273983,
Line 1328, P(1), 43.827878665924,Line 1328, P(2), 2.3331880249977,SS,
5.7149626687023,
Line 1145, P(1), 42.936904525757,Line 1145, P(2),
2.2860383016205,SS, 5.7103938877878,
Line 1328, P(1),
42.652888965607,Line 1328, P(2), 2.2703086389351,SS, 5.7144777202831,
Line 1145, P(1), 43.536077613831,Line 1145, P(2), 2.3174662152481,SS,
5.701514440077,
Line 1328, P(1), 43.843449649811,Line 1328, P(2),
2.3331723191261,SS, 5.7030893582732,
Line 1145, P(1),
42.952475509644,Line 1145, P(2), 2.2860225957489,SS, 5.6977719484345,
Line 1328, P(1), 42.668459949493,Line 1328, P(2), 2.2702929330635,SS,
5.7016129317414,
Line 1145, P(1), 43.551648597717,Line 1145, P(2),
2.3174505093765,SS, 5.6894076551537,
Line 1328, P(1),
43.859020633698,Line 1328, P(2), 2.3331566132545,SS, 5.6912407459458,
Line 1145, P(1), 42.96804649353,Line 1145, P(2), 2.2860068898773,SS,
5.6851765011912,
Line 1328, P(1), 42.68403093338,Line 1328, P(2),
2.2702772271919,SS, 5.6887752388486,
Line 1145, P(1),
43.567219581604,Line 1145, P(2), 2.3174348035049,SS, 5.6773261329376,
Line 1328, P(1), 43.874591617584,Line 1328, P(2), 2.333140907383,SS,
5.679416793366,
Line 1145, P(1), 42.983617477417,Line 1145, P(2),
2.2859911840057,SS, 5.6726075036728,
Line 1328, P(1),
42.699601917267,Line 1328, P(2), 2.2702615213203,SS, 5.6759645978291,
Line 1145, P(1), 43.582790565491,Line 1145, P(2), 2.3174190976334,SS,
5.6652698338087,
Line 1328, P(1), 43.890162601471,Line 1328, P(2),
2.3331252015114,SS, 5.6676174622478,
Line 1145, P(1),
42.999188461304,Line 1145, P(2), 2.2859754781341,SS, 5.6600649135707,
Line 1328, P(1), 42.715172901154,Line 1328, P(2), 2.2702458154488,SS,
5.6631809649873,
Line 1145, P(1), 43.598361549377,Line 1145, P(2),
2.3174033917618,SS, 5.6532387182176,
Line 1328, P(1),
43.905733585358,Line 1328, P(2), 2.3331094956398,SS, 5.655842714373,
Line
1145, P(1), 43.01475944519,Line 1145, P(2), 2.2859597722626,SS,
5.6475486886536,
Line 1328, P(1), 42.73074388504,Line 1328, P(2),
2.2702301095772,SS, 5.6504242967075,
Line 1145, P(1),
43.613932533264,Line 1145, P(2), 2.3173876858902,SS, 5.6412327466858,
Line 1328, P(1), 43.921304569244,Line 1328, P(2), 2.3330937897682,SS,
5.6440925115909,
Line 1145, P(1), 43.030330429077,Line 1145, P(2),
2.285944066391,SS, 5.6350587867666,
Line 1328, P(1), 42.746314868927,Line
1328, P(2), 2.2702144037056,SS, 5.637694549454,
Line 1145, P(1),
43.629503517151,Line 1145, P(2), 2.3173719800186,SS, 5.6292518798051,
Line 1328, P(1), 43.936875553131,Line 1328, P(2), 2.3330780838966,SS,
5.6323668158185,
Line 1145, P(1), 43.045901412964,Line 1145, P(2),
2.2859283605194,SS, 5.6225951658312,
Line 1328, P(1),
42.761885852814,Line 1328, P(2), 2.270198697834,SS, 5.6249916797707,
Line
1145, P(1), 43.645074501038,Line 1145, P(2), 2.317356274147,SS,
5.6172960782376,
Line 1328, P(1), 43.952446537018,Line 1328, P(2),
2.333062378025,SS, 5.6206655890401,
Line 1145, P(1), 43.061472396851,Line
1145, P(2), 2.2859126546478,SS, 5.6101577838456,
Line 1328, P(1),
42.7774568367,Line 1328, P(2), 2.2701829919624,SS, 5.612315644281,
Line
1145, P(1), 43.660645484924,Line 1145, P(2), 2.3173405682754,SS,
5.6053653027156,
Line 1328, P(1), 43.968017520905,Line 1328, P(2),
2.3330466721535,SS, 5.6089887933074,
Line 1145, P(1),
43.077043380737,Line 1145, P(2), 2.2858969487762,SS, 5.597746598884,
Line
1328, P(1), 42.793027820587,Line 1328, P(2), 2.2701672860908,SS,
5.5996663996878,
Line 1145, P(1), 43.676216468811,Line 1145, P(2),
2.3173248624039,SS, 5.5934595140416,
Line 1328, P(1),
43.983588504791,Line 1328, P(2), 2.3330309662819,SS, 5.5973363907391,
Line 1145, P(1), 43.092614364624,Line 1145, P(2), 2.2858812429047,SS,
5.5853615690967,
Line 1328, P(1), 42.808598804474,Line 1328, P(2),
2.2701515802193,SS, 5.5870439027731,
Line 1145, P(1),
43.691787452698,Line 1145, P(2), 2.3173091565323,SS, 5.581578673088,
Line
1328, P(1), 43.999159488678,Line 1328, P(2), 2.3330152604103,SS,
5.585708343521,
Line 1145, P(1), 43.108185348511,Line 1145, P(2),
2.2858655370331,SS, 5.5730026527099,
Line 1328, P(1),
42.824169788361,Line 1328, P(2), 2.2701358743477,SS, 5.5744481103979,
Line 1145, P(1), 43.707358436585,Line 1145, P(2), 2.3172934506607,SS,
5.5697227407968,
Line 1328, P(1), 44.014730472565,Line 1328, P(2),
2.3329995545387,SS, 5.5741046139057,
Line 1145, P(1),
43.123756332398,Line 1145, P(2), 2.2858498311615,SS, 5.5606698080255,
Line 1328, P(1), 42.839740772247,Line 1328, P(2), 2.2701201684761,SS,
5.5618789795022,
Line 1145, P(1), 43.722929420471,Line 1145, P(2),
2.3172777447891,SS, 5.55789167818,
Line 1328, P(1), 44.030301456451,Line
1328, P(2), 2.3329838486671,SS, 5.5625251642127,
Line 1145, P(1),
43.139327316284,Line 1145, P(2), 2.2858341252899,SS, 5.5483629934213,
Line 1328, P(1), 42.855311756134,Line 1328, P(2), 2.2701044626045,SS,
5.5493364671046,
Line 1145, P(1), 43.738500404358,Line 1145, P(2),
2.3172620389175,SS, 5.5460854463187,
Line 1328, P(1),
44.045872440338,Line 1328, P(2), 2.3329681427955,SS, 5.550969956828,
Line
1145, P(1), 43.154898300171,Line 1145, P(2), 2.2858184194183,SS,
5.5360821673502,
Line 1328, P(1), 42.870882740021,Line 1328, P(2),
2.2700887567329,SS, 5.5368205303024,
Line 1145, P(1),
43.754071388245,Line 1145, P(2), 2.3172463330459,SS, 5.5343040063638,
Line 1328, P(1), 44.061443424225,Line 1328, P(2), 2.332952436924,SS,
5.5394389542041,
Line 1145, P(1), 43.170469284058,Line 1145, P(2),
2.2858027135467,SS, 5.5238272883405,
Line 1328, P(1),
42.886453723908,Line 1328, P(2), 2.2700730508613,SS, 5.5243311262713,
Line 1145, P(1), 43.769642372131,Line 1145, P(2), 2.3172306271744,SS,
5.5225473195353,
Line 1328, P(1), 44.077014408112,Line 1328, P(2),
2.3329367310524,SS, 5.52793211886,
Line 1145, P(1), 43.186040267944,Line
1145, P(2), 2.2857870076752,SS, 5.5115983149959,
Line 1328, P(1),
42.902024707794,Line 1328, P(2), 2.2700573449898,SS, 5.5118682122652,
Line 1145, P(1), 43.785213356018,Line 1145, P(2), 2.3172149213028,SS,
5.5108153471221,
Line 1328, P(1), 44.092585391998,Line 1328, P(2),
2.3329210251808,SS, 5.5164494133808,
Line 1145, P(1),
43.201611251831,Line 1145, P(2), 2.2857713018036,SS, 5.4993952059948,
Line 1328, P(1), 42.917595691681,Line 1328, P(2), 2.2700416391182,SS,
5.4994317456161,
Line 1145, P(1), 43.800784339905,Line 1145, P(2),
2.3171992154312,SS, 5.4991080504823,
Line 1328, P(1),
44.108156375885,Line 1328, P(2), 2.3329053193092,SS, 5.5049908004178,
Line 1145, P(1), 43.217182235718,Line 1145, P(2), 2.285755595932,SS,
5.4872179200908,
Line 1328, P(1), 42.933166675568,Line 1328, P(2),
2.2700259332466,SS, 5.4870216837339,
Line 1145, P(1),
43.532339763641,Line 1145, P(2), 2.3014538468742,SS, 5.4714128927259,
Line 1328, P(1), 43.697704019547,Line 1328, P(2), 2.3092951194095,SS,
5.4608532866156,
Line 1145, P(1), 42.830086355209,Line 1145, P(2),
2.2621218372249,SS, 5.4587402850935,
Line 1328, P(1),
42.344737362862,Line 1328, P(2), 2.2345831481218,SS, 5.474753475181,
Line
1145, P(1), 43.594623699188,Line 1145, P(2), 2.3013910233879,SS,
5.4240601225389,
Line 1328, P(1), 43.925352210999,Line 1328, P(2),
2.3170735684585,SS, 5.4063333908356,
Line 1145, P(1),
43.057734546662,Line 1145, P(2), 2.2699002862739,SS, 5.3886866750888,
Line 1328, P(1), 42.737749810219,Line 1328, P(2), 2.2502028697061,SS,
5.3694820692035,
Line 1145, P(1), 43.833015666008,Line 1145, P(2),
2.3051546009397,SS, 5.3028778439483,
Line 1328, P(1),
44.334480321408,Line 1328, P(2), 2.3266709827971,SS, 5.2545087768466,
Line 1145, P(1), 43.146877920628,Line 1145, P(2), 2.2598002840447,SS,
5.1841114198348,
Line 1328, P(1), 42.757640775442,Line 1328, P(2),
2.2311636418378,SS, 5.1049459362938,
Line 1145, P(1),
44.354371286631,Line 1145, P(2), 2.3076317549288,SS, 4.9734954496134,
Line 1328, P(1), 45.162682024837,Line 1328, P(2), 2.3363461975401,SS,
4.8453902205145,
Line 1145, P(1), 43.585842478872,Line 1145, P(2),
2.2408388565808,SS, 4.6253930111353,
Line 1328, P(1),
43.211523557604,Line 1328, P(2), 2.1979227934726,SS, 4.3788930043702,
Line 1145, P(1), 45.616564806999,Line 1145, P(2), 2.3031053491749,SS,
4.1372031701753,
Line 1328, P(1), 47.046026822777,Line 1328, P(2),
2.3390762028435,SS, 3.8474943355714,
Line 1145, P(1),
45.094868355544,Line 1145, P(2), 2.200652798776,SS, 3.2802654655555,
Line
1328, P(1), 45.060961520898,Line 1328, P(2), 2.1328060993939,SS,
2.7315358801379,
Line 1145, P(1), 48.89546478607,Line 1145, P(2),
2.2739595087648,SS, 2.4249539395526,
Line 1328, P(1),
51.737435400303,Line 1328, P(2), 2.3119778664109,SS, 2.072195650346,
Line
1145, P(1), 49.752370098424,Line 1145, P(2), 2.1057077629613,SS,
1.2159257505702,
Line 1328, P(1), 51.105541736248,Line 1328, P(2),
1.9890235430203,SS, 1.0958686066734,
Line 1145, P(1),
57.782015615653,Line 1145, P(2), 2.1681953100372,SS, 1.2205333189555,
Line 1145, P(1), 57.150121951598,Line 1145, P(2), 1.8452409866466,SS,
2.5930669098556,
Line 1205, P(1), 53.090607038127,Line 1205, P(2),
2.1952936464698,SS, 1.1767331846374,
Line 1145, P(1),
46.414133158721,Line 1145, P(2), 2.0161218794529,SS, 1.7589265024691,
Line 1205, P(1), 54.94004500142,Line 1205, P(2), 2.1301769523911,SS,
0.99002152679945,
Line 1145, P(1), 52.954979699541,Line 1145, P(2),
1.9239068489416,SS, 1.4193763923201,
Line 1205, P(1), 53.05670020348,Line
1205, P(2), 2.1274469470878,SS, 0.97798782911144,
Line 1145, P(1),
56.891203468653,Line 1145, P(2), 2.2686003564586,SS, 1.450452979839,
Line
1205, P(1), 52.551957169349,Line 1205, P(2), 2.0589177463799,SS,
0.94499257497941,
Line 1145, P(1), 50.668612371409,Line 1145, P(2),
2.0561877410765,SS, 1.0351107008244,
Line 1205, P(1),
53.872186843918,Line 1205, P(2), 2.1116796495625,SS, 0.95004251376904,
Line 1145, P(1), 53.367443809786,Line 1145, P(2), 2.0431504488546,SS,
0.96509530579689,
Line 1205, P(1), 53.28975790821,Line 1205, P(2),
2.0642245734129,SS, 0.9405634062128,
Line 1145, P(1),
51.969528233641,Line 1145, P(2), 2.0114626702303,SS, 1.0185422885338,
Line 1205, P(1), 53.396522191348,Line 1205, P(2), 2.0866254047294,SS,
0.935099500333,
Line 1145, P(1), 54.134322930209,Line 1145, P(2),
2.0919322317624,SS, 0.94614099589987,
Line 1205, P(1),
52.947548609564,Line 1205, P(2), 2.0671713677255,SS, 0.93777309002651,
Line 1145, P(1), 53.054312892703,Line 1145, P(2), 2.0895721990421,SS,
0.93682623850727,
Line 1145, P(1), 53.503286474487,Line 1145, P(2),
2.109026236046,SS, 0.9467153761271,
Line 1205, P(1), 53.086483075795,Line
1205, P(2), 2.0776350848056,SS, 0.93477313711805,
Line 1145, P(1),
53.42869237444,Line 1145, P(2), 2.074688290493,SS, 0.9365937680499,
Line
1205, P(1), 53.335097504006,Line 1205, P(2), 2.0784092676303,SS,
0.93496530244541,
Line 1145, P(1), 53.025058388452,Line 1145, P(2),
2.0694189477065,SS, 0.93672335990035,
Line 1205, P(1),
53.303656240624,Line 1205, P(2), 2.0823237904737,SS, 0.93454541585904,
Line 1145, P(1), 53.055041812413,Line 1145, P(2), 2.081549607649,SS,
0.93492189448704,
Line 1205, P(1), 53.125055735311,Line 1205, P(2),
2.0807645226443,SS, 0.93457549512653,
Line 1145, P(1),
53.342228900141,Line 1145, P(2), 2.0854532283124,SS, 0.93480530874824,
Line 1205, P(1), 53.150419531881,Line 1205, P(2), 2.0795896206823,SS,
0.93452256625145,
Line 1145, P(1), 53.329020037194,Line 1145, P(2),
2.0811488885116,SS, 0.93465116829766,
Line 1205, P(1),
53.176046810782,Line 1205, P(2), 2.0808606141112,SS, 0.93446860532377,
Line 1145, P(1), 53.022810102039,Line 1145, P(2), 2.0781264443198,SS,
0.93500669605026,
Line 1205, P(1), 53.233444705978,Line 1205, P(2),
2.0812744539352,SS, 0.93444565733895,
Line 1145, P(1),
53.259071984879,Line 1145, P(2), 2.0825454473641,SS, 0.93447892772237,
Line 1205, P(1), 53.231908871629,Line 1205, P(2), 2.0818064906936,SS,
0.93444807501061,
Line 1145, P(1), 53.289306766825,Line 1145, P(2),
2.0822203305177,SS, 0.93451390979108,
Line 1205, P(1),
53.204361799793,Line 1205, P(2), 2.0812005432128,SS, 0.9344455326232,
Line 998, P(1), 53.233444705978,Line 998, P(2), 2.0812744539352,SS,
0.93444565733895,
Third Run.
Line 936, P(1), 53.95,Line 936, P(2),
2.875535,SS, 9.3643499409975,
Line 936, P(1), 107.895,Line 936, P(2),
0.005,SS, 77.165687432929,
Line 936, P(1), 0.005,Line 936, P(2),
0.005,SS, 794447644.86191,
Line 1145, P(1), 161.84,Line 1145, P(2),
2.875535,SS, 59.48077956873,
Line 1145, P(1), 107.895,Line 1145, P(2),
5.74607,SS, 59.427684204339,
Line 1145, P(1), 0.0049999999999955,Line
1145, P(2), 5.74607,SS, 459.81413559632,
Line 1205, P(1), 121.38125,Line
1205, P(2), 3.59316875,SS, 32.950202226101,
Line 1145, P(1),
67.43625,Line 1145, P(2), 0.72263375,SS, 49.767615792294,
Line 1205,
P(1), 77.5509375,Line 1205, P(2), 1.9784928125,SS, 7.2804827205959,
Line
1145, P(1), 10.1196875,Line 1145, P(2), 1.2608590625,SS, 506.9310429502,
Line 1205, P(1), 93.565859375,Line 1205, P(2), 3.010091328125,SS,
15.068947850109,
Line 1145, P(1), 37.935078125,Line 1145, P(2),
1.843936484375,SS, 6.6451137071563,
Line 1328, P(1), 10.1196875,Line
1328, P(2), 1.2608590625,SS, 506.9310429502,
Line 1145, P(1),
61.536015625,Line 1145, P(2), 0.946894296875,SS, 36.197614672385,
Line
1205, P(1), 55.84650390625,Line 1205, P(2), 2.3933748242187,SS,
2.2719938098741,
Line 1145, P(1), 16.23064453125,Line 1145, P(2),
2.2588184960937,SS, 176.54760429402,
Line 1205, P(1),
62.220864257813,Line 1205, P(2), 2.0485742333984,SS, 2.1146885917274,
Line 1145, P(1), 80.132290039063,Line 1145, P(2), 2.5980125732422,SS,
7.7235358840136,
Line 1205, P(1), 48.484381103516,Line 1205, P(2),
2.0324555065918,SS, 1.304963989426,
Line 1145, P(1), 54.858741455078,Line
1145, P(2), 1.6876549157715,SS, 4.5756312834065,
Line 1205, P(1),
55.599563293457,Line 1205, P(2), 2.2169448471069,SS, 1.2089353508824,
Line 1145, P(1), 41.86308013916,Line 1145, P(2), 2.2008261203003,SS,
5.4351280011819,
Line 1205, P(1), 57.131418228149,Line 1205, P(2),
2.0866372051239,SS, 1.1573177461889,
Line 1145, P(1),
64.246600418091,Line 1145, P(2), 2.271126545639,SS, 2.350146537873,
Line
1205, P(1), 52.424935932159,Line 1205, P(2), 2.0921232663536,SS,
0.95154870321105,
Line 1145, P(1), 53.956790866852,Line 1145, P(2),
1.9618156243706,SS, 1.260679014386,
Line 1205, P(1), 55.188870186806,Line
1205, P(2), 2.1531625414228,SS, 1.0296540688787,
Line 1145, P(1),
50.482387890816,Line 1145, P(2), 2.1586486026525,SS, 1.2911208226028,
Line 1205, P(1), 55.469160643816,Line 1205, P(2), 2.1046400545061,SS,
1.0027710099626,
Line 1145, P(1), 52.70522638917,Line 1145, P(2),
2.0436007794368,SS, 0.95773328789682,
Line 1145, P(1),
49.661001677513,Line 1145, P(2), 2.0310839912844,SS, 1.1361157646104,
Line 1205, P(1), 54.01712090224,Line 1205, P(2), 2.0862510387006,SS,
0.94369520747692,
Line 1145, P(1), 53.73683044523,Line 1145, P(2),
2.1347735256174,SS, 0.97945030830136,
Line 1205, P(1),
52.963127403185,Line 1205, P(2), 2.066393965982,SS, 0.93807264855818,
Line 1145, P(1), 54.555312373266,Line 1145, P(2), 2.060521738329,SS,
0.98304848962129,
Line 1205, P(1), 52.957530042436,Line 1205, P(2),
2.0842228843475,SS, 0.93612192917216,
Line 1145, P(1),
51.90353654338,Line 1145, P(2), 2.0643658116288,SS, 0.96014302445733,
Line 1205, P(1), 53.488724812525,Line 1205, P(2), 2.0807797319327,SS,
0.93572044128753,
Line 1145, P(1), 53.483127451777,Line 1145, P(2),
2.0986086502982,SS, 0.93924744926754,
Line 1205, P(1),
53.093127415333,Line 1205, P(2), 2.074447637061,SS, 0.93520646207316,
Line 1145, P(1), 53.624322185422,Line 1145, P(2), 2.0710044846462,SS,
0.94096499472579,
Line 1205, P(1), 53.124228078182,Line 1205, P(2),
2.0809182844222,SS, 0.93458213226399,
Line 1145, P(1),
52.72863068099,Line 1145, P(2), 2.0745861895505,SS, 0.9379398420121,
Line
1205, P(1), 53.298701279641,Line 1205, P(2), 2.0792313463371,SS,
0.93469619037625,
Line 1145, P(1), 53.329801942491,Line 1145, P(2),
2.0857019936983,SS, 0.93480796323906,
Line 1205, P(1),
53.270633310702,Line 1205, P(2), 2.082888404539,SS, 0.93450159245283,
Line 1145, P(1), 53.096160109243,Line 1145, P(2), 2.084575342624,SS,
0.93509043152948,
Line 1205, P(1), 53.248065987042,Line 1205, P(2),
2.0805673454088,SS, 0.93447373344692,
Line 1145, P(1),
53.394471219561,Line 1145, P(2), 2.0825374655256,SS, 0.93489242035072,
Line 1205, P(1), 53.191788863527,Line 1205, P(2), 2.081323079698,SS,
0.934455728052,
Line 1145, P(1), 53.169221539867,Line 1145, P(2),
2.0790020205679,SS, 0.93452901585447,
Line 1205, P(1),
53.245280367993,Line 1205, P(2), 2.0819168085462,SS, 0.93445498665899,
Line 1145, P(1), 53.189003244478,Line 1145, P(2), 2.0826725428354,SS,
0.93451536880618,
Line 1205, P(1), 53.233300301401,Line 1205, P(2),
2.0810936447655,SS, 0.93444707936235,
Line 998, P(1),
53.245280367993,Line 998, P(2), 2.0819168085462,SS, 0.93445498665899,
Fourth run.
This run settled on a local minimum.
Line 936, P(1), 53.95,Line 936, P(2), 2.875535,SS, 9.3643499409975,
Line
936, P(1), 0.005,Line 936, P(2), 0.005,SS, 794447644.86191,
Line 936,
P(1), 0.005,Line 936, P(2), 0.005,SS, 794447644.86191,
Line 1145, P(1),
53.95,Line 1145, P(2), 2.875535,SS, 9.3643499409975,
Line 1145, P(1),
107.895,Line 1145, P(2), 5.74607,SS, 59.427684204339,
Line 1205, P(1),
80.9225,Line 1205, P(2), 4.3108025,SS, 30.696175844464,
Line 1145, P(1),
26.9775,Line 1145, P(2), 1.4402675,SS, 34.616417584274,
Line 1205, P(1),
67.43625,Line 1205, P(2), 3.59316875,SS, 18.878553455022,
Line 1145,
P(1), 40.46375,Line 1145, P(2), 2.15790125,SS, 6.1543482056666,
Line
1328, P(1), 26.9775,Line 1328, P(2), 1.4402675,SS, 34.616417584274,
Line
1145, P(1), 40.46375,Line 1145, P(2), 2.15790125,SS, 6.1543482056666,
Line 1145, P(1), 26.9775,Line 1145, P(2), 1.4402675,SS, 34.616417584274,
Line 1205, P(1), 47.206875,Line 1205, P(2), 2.516718125,SS, 6.3719463828936,
Line 1145, P(1), 33.720625,Line 1145, P(2), 1.799084375,SS, 12.254534489363,
Line 1205, P(1), 43.8353125,Line 1205, P(2), 2.3373096875,SS,
5.7713600574563,
Line 1145, P(1), 43.8353125,Line 1145, P(2),
2.3373096875,SS, 5.7713600574563,
Line 1145, P(1), 47.206875,Line 1145,
P(2), 2.516718125,SS, 6.3719463828936,
Line 1205, P(1), 42.14953125,Line
1205, P(2), 2.24760546875,SS, 5.8136340873439,
Line 1145, P(1),
45.52109375,Line 1145, P(2), 2.42701390625,SS, 5.9720670111166,
Line
1205, P(1), 42.992421875,Line 1205, P(2), 2.292457578125,SS,
5.7589674713107,
Line 1145, P(1), 42.992421875,Line 1145, P(2),
2.292457578125,SS, 5.7589674713107,
Line 1145, P(1), 42.14953125,Line
1145, P(2), 2.24760546875,SS, 5.8136340873439,
Line 1205, P(1),
43.4138671875,Line 1205, P(2), 2.3148836328125,SS, 5.7572052705037,
Line
1145, P(1), 43.4138671875,Line 1145, P(2), 2.3148836328125,SS,
5.7572052705037,
Line 1145, P(1), 43.8353125,Line 1145, P(2),
2.3373096875,SS, 5.7713600574563,
Line 1205, P(1), 43.20314453125,Line
1205, P(2), 2.3036706054688,SS, 5.7560457216644,
Line 1145, P(1),
43.20314453125,Line 1145, P(2), 2.3036706054688,SS, 5.7560457216644,
Line
1145, P(1), 42.992421875,Line 1145, P(2), 2.292457578125,SS,
5.7589674713107,
Line 1205, P(1), 43.308505859375,Line 1205, P(2),
2.3092771191406,SS, 5.7561218302541,
Line 1145, P(1),
43.097783203125,Line 1145, P(2), 2.2980640917969,SS, 5.7569898893036,
Line 1205, P(1), 43.255825195313,Line 1205, P(2), 2.3064738623047,SS,
5.7559570549659,
Line 998, P(1), 43.20314453125,Line 998, P(2),
2.3036706054688,SS, 5.7560457216644,
Fifth run.
Line 936, P(1),
53.95,Line 936, P(2), 2.875535,SS, 9.3643499409975,
Line 936, P(1),
107.905,Line 936, P(2), 5.75607,SS, 59.622407046901,
Line 936, P(1),
107.905,Line 936, P(2), 0.005,SS, 77.162380802885,
Line 1145, P(1),
53.95,Line 1145, P(2), 8.626605,SS, 136.5010734589,
Line 1205, P(1),
94.41625,Line 1205, P(2), 2.16040125,SS, 13.551114625175,
Line 1145,
P(1), 40.46125,Line 1145, P(2), 0.72013375,SS, 91.239467914442,
Line
1205, P(1), 91.0440625,Line 1205, P(2), 4.1370190625,SS, 28.163712901957,
Line 1145, P(1), 57.3221875,Line 1145, P(2), 0.8989171875,SS,
42.038808091378,
Line 1205, P(1), 82.61359375,Line 1205, P(2),
3.32749359375,SS, 14.980875702201,
Line 1145, P(1), 65.75265625,Line
1145, P(2), 1.70844265625,SS, 6.5078970933167,
Line 1328, P(1),
57.3221875,Line 1328, P(2), 0.8989171875,SS, 42.038808091378,
Line 1145,
P(1), 25.28640625,Line 1145, P(2), 2.42357640625,SS, 60.91340520219,
Line
1205, P(1), 77.1337890625,Line 1205, P(2), 2.2261950390625,SS,
6.0365380792999,
Line 1145, P(1), 88.9364453125,Line 1145, P(2),
1.0591026953125,SS, 29.478756800474,
Line 1205, P(1),
62.696611328125,Line 1205, P(2), 2.4214269238281,SS, 2.7146658906355,
Line 1145, P(1), 74.077744140625,Line 1145, P(2), 2.9391793066406,SS,
8.8796467859504,
Line 1205, P(1), 67.833928222656,Line 1205, P(2),
2.0161268188477,SS, 3.7293438847807,
Line 1145, P(1),
53.396750488281,Line 1145, P(2), 2.2113587036133,SS, 1.2277669931083,
Line 1328, P(1), 41.528231201172,Line 1328, P(2), 2.2039405358887,SS,
5.7611830340079,
Line 1145, P(1), 48.25943359375,Line 1145, P(2),
2.6166588085937,SS, 7.4770910189701,
Line 1205, P(1), 62.94030456543,Line
1205, P(2), 2.1662598162842,SS, 2.0090195854269,
Line 1145, P(1),
53.640443725586,Line 1145, P(2), 1.9561915960693,SS, 1.2692245065489,
Line 1145, P(1), 44.096889648438,Line 1145, P(2), 2.0012904833984,SS,
2.5583822473677,
Line 1205, P(1), 58.229450836182,Line 1205, P(2),
2.1250174830627,SS, 1.2525990724923,
Line 1145, P(1),
57.985757598877,Line 1145, P(2), 2.3801845906067,SS, 2.1242935196303,
Line 1205, P(1), 54.726772193909,Line 1205, P(2), 2.0621898447037,SS,
0.98987108511765,
Line 1145, P(1), 49.894071846008,Line 1145, P(2),
2.1485310652542,SS, 1.342241305278,
Line 1205, P(1), 56.145606088638,Line
1205, P(2), 2.1308958786106,SS, 1.0525868164066,
Line 1145, P(1),
57.475627794266,Line 1145, P(2), 1.981727019701,SS, 1.5448461154734,
Line
1205, P(1), 54.416469814777,Line 1205, P(2), 2.1539507826352,SS,
1.0160234471732,
Line 1145, P(1), 52.997635920048,Line 1145, P(2),
2.0852447487283,SS, 0.93597390062612,
Line 1328, P(1),
51.423650835753,Line 1328, P(2), 2.0624191837871,SS, 0.98305621411454,
Line 1145, P(1), 53.307938299179,Line 1145, P(2), 1.9934838107967,SS,
1.0887896387288,
Line 1205, P(1), 54.139336935878,Line 1205, P(2),
2.1138340396756,SS, 0.95504401818513,
Line 1145, P(1),
52.410200662017,Line 1145, P(2), 2.1368889437002,SS, 1.0243664226278,
Line 1205, P(1), 54.147629310936,Line 1205, P(2), 2.0808646194528,SS,
0.94875431653599,
Line 1145, P(1), 53.005928295106,Line 1145, P(2),
2.0522753285055,SS, 0.94858386628582,
Line 1145, P(1),
51.855934904218,Line 1145, P(2), 2.056655457781,SS, 0.96344688535051,
Line 1205, P(1), 53.574705709256,Line 1205, P(2), 2.0748123290348,SS,
0.93833262233659,
Line 1145, P(1), 53.566413334198,Line 1145, P(2),
2.1077817492576,SS, 0.94554351597948,
Line 1205, P(1),
53.426292074425,Line 1205, P(2), 2.0939051440696,SS, 0.93702302665939,
Line 1145, P(1), 52.849222285217,Line 1145, P(2), 2.104337563763,SS,
0.95067197457554,
Line 1205, P(1), 53.393334853246,Line 1205, P(2),
2.0821936377169,SS, 0.93489807285589,
Line 1145, P(1),
52.964678698869,Line 1145, P(2), 2.0735332423756,SS, 0.93579814720358,
Line 1145, P(1), 53.360377632068,Line 1145, P(2), 2.0704821313642,SS,
0.93763944709127,
Line 1205, P(1), 53.088321348053,Line 1205, P(2),
2.0815540943873,SS, 0.93475110277835,
Line 1145, P(1),
53.51697750243,Line 1145, P(2), 2.0902144897286,SS, 0.93627218632108,
Line 1205, P(1), 53.102753399759,Line 1205, P(2), 2.0777035542138,SS,
0.93472484030069,
Line 1145, P(1), 52.797739894566,Line 1145, P(2),
2.0770640108842,SS, 0.93701821376355,
Line 1205, P(1),
53.244436113576,Line 1205, P(2), 2.0809112310087,SS, 0.93445898602524,
Line 1145, P(1), 53.258868165283,Line 1145, P(2), 2.0770606908353,SS,
0.934872827227,
Line 1205, P(1), 53.13095805236,Line 1205, P(2),
2.0804307434993,SS, 0.93455360206149,
Line 1145, P(1),
53.272640766177,Line 1145, P(2), 2.0836384202942,SS, 0.93454339752292,
Line 1145, P(1), 53.386118827393,Line 1145, P(2), 2.0841189078036,SS,
0.93485777426806,
Line 1205, P(1), 53.194748246118,Line 1205, P(2),
2.0813527845753,SS, 0.93445349726254,
Line 1145, P(1),
53.166543593517,Line 1145, P(2), 2.0786255952899,SS, 0.9345568067241,
Line 1205, P(1), 53.246116473012,Line 1205, P(2), 2.0823852140431,SS,
0.9344661050463,
Line 1145, P(1), 53.193067886682,Line 1145, P(2),
2.079878801541,SS, 0.93447265861826,
Line 1205, P(1), 53.23285432643,Line
1205, P(2), 2.0817586109176,SS, 0.93444757286484,
Line 998, P(1),
53.194748246118,Line 998, P(2), 2.0813527845753,SS, 0.93445349726254,
The same patient data was used, but the actual steady state serum levels
were a peak of 46 mcg/ml and trough on 5 mcg/ml, analyzed using the Bayesian
SSE method. The initial parameter estimate for the patient were Vd 53.95 and
clearance 2.875535. Finally estimates for each run can be seen below with a
Vd of ~ 32.8 Liters and clearance of 3.35 L/Hr . The
Bayesian estimated levels were a peak 45.29 mcg/ml, trough 4.8 mcg/ml, and AUC 448.4.
First run settled on a local minimum. Line 936,
P(1), 53.95,Line 936, P(2), 2.875535,SS, 102.22541693667,
Line 936, P(1),
107.895,Line 936, P(2), 5.75607,SS, 61.811927963931,
Line 936, P(1),
107.895,Line 936, P(2), 5.75607,SS, 61.811927963931,
Line 1145, P(1),
161.84,Line 1145, P(2), 8.636605,SS, 142.67174745812,
Line 1205, P(1),
80.9225,Line 1205, P(2), 4.3158025,SS, 48.499611583126,
Line 1145, P(1),
80.9225,Line 1145, P(2), 4.3158025,SS, 48.499611583126,
Line 1328, P(1),
67.43625,Line 1328, P(2), 3.59566875,SS, 59.62850372617,
Line 1145, P(1),
53.95,Line 1145, P(2), 2.875535,SS, 102.22541693667,
Line 1205, P(1),
94.40875,Line 1205, P(2), 5.03593625,SS, 51.382532632491,
Line 1145,
P(1), 67.43625,Line 1145, P(2), 3.59566875,SS, 59.62850372617,
Line 1205,
P(1), 87.665625,Line 1205, P(2), 4.675869375,SS, 48.727038726216,
Line
1145, P(1), 74.179375,Line 1145, P(2), 3.955735625,SS, 51.631415864491,
Line 1205, P(1), 84.2940625,Line 1205, P(2), 4.4958359375,SS,
48.261637255358,
Line 1145, P(1), 84.2940625,Line 1145, P(2),
4.4958359375,SS, 48.261637255358,
Line 1328, P(1), 85.97984375,Line 1328,
P(2), 4.58585265625,SS, 48.413296157117,
Line 1145, P(1), 87.665625,Line
1145, P(2), 4.675869375,SS, 48.727038726216,
Line 1205, P(1),
82.60828125,Line 1205, P(2), 4.40581921875,SS, 48.285414278867,
Line
1145, P(1), 85.97984375,Line 1145, P(2), 4.58585265625,SS, 48.413296157117,
Line 1205, P(1), 83.451171875,Line 1205, P(2), 4.450827578125,SS,
48.250700536102,
Line 1145, P(1), 83.451171875,Line 1145, P(2),
4.450827578125,SS, 48.250700536102,
Line 1328, P(1), 83.0297265625,Line
1328, P(2), 4.4283233984375,SS, 48.262233382032,
Line 1145, P(1),
82.60828125,Line 1145, P(2), 4.40581921875,SS, 48.285414278867,
Line
1205, P(1), 83.8726171875,Line 1205, P(2), 4.4733317578125,SS,
48.250578608877,
Line 1145, P(1), 83.8726171875,Line 1145, P(2),
4.4733317578125,SS, 48.250578608877,
Line 998, P(1), 83.8726171875,Line
998, P(2), 4.4733317578125,SS, 48.250578608877,
Second run.
Line 936, P(1),
53.95,Line 936, P(2), 2.875535,SS, 102.22541693667,
Line 936, P(1),
0.005,Line 936, P(2), 5.74607,SS, 459.81413559632,
Line 936, P(1),
0.005,Line 936, P(2), 5.75607,SS, 458.0822613329,
Line 1145, P(1),
53.95,Line 1145, P(2), 2.885535,SS, 100.67402505225,
Line 1328, P(1),
80.9225,Line 1328, P(2), 1.4552675,SS, 481.30119037992,
Line 1145, P(1),
107.895,Line 1145, P(2), 0.0049999999999999,SS, 827.76556654884,
Line
1205, P(1), 26.9775,Line 1205, P(2), 4.3183025,SS, 52.134558471144,
Line
1145, P(1), 26.9775,Line 1145, P(2), 4.3283025,SS, 52.530843811258,
Line
1145, P(1), 0.0050000000000097,Line 1145, P(2), 5.76107,SS, 457.22059642023,
Line 1205, P(1), 40.46375,Line 1205, P(2), 3.60441875,SS, 5.8657792157338,
Line 1145, P(1), 40.46375,Line 1145, P(2), 3.59441875,SS, 5.9906726584848,
Line 1145, P(1), 53.95,Line 1145, P(2), 2.880535,SS, 101.44718066194,
Line 1205, P(1), 33.720625,Line 1205, P(2), 3.958860625,SS, 12.761190743305,
Line 1145, P(1), 47.206875,Line 1145, P(2), 3.239976875,SS, 37.547266065674,
Line 1205, P(1), 37.0921875,Line 1205, P(2), 3.7791396875,SS,
4.5307639533244,
Line 1145, P(1), 37.0921875,Line 1145, P(2),
3.7891396875,SS, 4.6688989124325,
Line 1145, P(1), 33.720625,Line 1145,
P(2), 3.963860625,SS, 12.919829787843,
Line 1205, P(1), 38.77796875,Line
1205, P(2), 3.69427921875,SS, 4.0004120014745,
Line 1145, P(1),
38.77796875,Line 1145, P(2), 3.68427921875,SS, 3.9865603597601,
Line
1328, P(1), 39.620859375,Line 1328, P(2), 3.631848984375,SS,
4.7233481190556,
Line 1145, P(1), 40.46375,Line 1145, P(2),
3.59941875,SS, 5.9271011171454,
Line 1205, P(1), 37.935078125,Line 1205,
P(2), 3.734209453125,SS, 3.954201319521,
Line 1145, P(1),
37.935078125,Line 1145, P(2), 3.724209453125,SS, 3.8805913768085,
Line
1328, P(1), 37.5136328125,Line 1328, P(2), 3.7391745703125,SS,
3.9888045560025,
Line 1145, P(1), 37.0921875,Line 1145, P(2),
3.7741396875,SS, 4.4638392550962,
Line 1205, P(1), 38.3565234375,Line
1205, P(2), 3.7067443359375,SS, 3.8740702635857,
Line 1145, P(1),
38.3565234375,Line 1145, P(2), 3.6967443359375,SS, 3.835139483197,
Line
1328, P(1), 38.56724609375,Line 1328, P(2), 3.6780117773438,SS,
3.8757769857426,
Line 1145, P(1), 38.77796875,Line 1145, P(2),
3.67927921875,SS, 3.9824069670876,
Line 1205, P(1), 38.14580078125,Line
1205, P(2), 3.7129768945313,SS, 3.8477440019968,
Line 1145, P(1),
38.14580078125,Line 1145, P(2), 3.7029768945313,SS, 3.7964300664561,
Line
1328, P(1), 38.040439453125,Line 1328, P(2), 3.7010931738281,SS,
3.7602733932483,
Line 1145, P(1), 38.251162109375,Line 1145, P(2),
3.6848606152344,SS, 3.7582324067894,
Line 1328, P(1),
38.303842773438,Line 1328, P(2), 3.6708024755859,SS, 3.7444460681769,
Line 1145, P(1), 37.987758789063,Line 1145, P(2), 3.6751513134766,SS,
3.6351048746402,
Line 1328, P(1), 37.803376464844,Line 1328, P(2),
3.6643548022461,SS, 3.5385019562444,
Line 1145, P(1),
38.066779785156,Line 1145, P(2), 3.6340641040039,SS, 3.5974970090065,
Line 1145, P(1), 37.566313476563,Line 1145, P(2), 3.6276164306641,SS,
3.362432851062,
Line 1328, P(1), 37.197548828125,Line 1328, P(2),
3.6060234082031,SS, 3.1855988095988,
Line 1145, P(1),
36.934145507813,Line 1145, P(2), 3.6363141064453,SS, 3.2064386277202,
Line 1145, P(1), 36.328317871094,Line 1145, P(2), 3.5779827124023,SS,
2.8559391010594,
Line 1328, P(1), 35.590788574219,Line 1328, P(2),
3.5347966674805,SS, 2.5822652280832,
Line 1145, P(1),
35.854191894531,Line 1145, P(2), 3.5045059692383,SS, 2.6324492410046,
Line 1145, P(1), 34.247431640625,Line 1145, P(2), 3.4332792285156,SS,
2.1865730599097,
Line 1328, P(1), 32.772373046875,Line 1328, P(2),
3.3469071386719,SS, 2.041455569965,
Line 1145, P(1), 32.508969726563,Line
1145, P(2), 3.3771978369141,SS, 2.164168312138,
Line 1145, P(1),
29.690554199219,Line 1145, P(2), 3.1893083081055,SS, 2.9334641836844,
Line 1205, P(1), 34.115729980469,Line 1205, P(2), 3.4484245776367,SS,
2.19751958802,
Line 1145, P(1), 31.165612792969,Line 1145, P(2),
3.2756803979492,SS, 2.2895652670931,
Line 1205, P(1),
33.378200683594,Line 1205, P(2), 3.4052385327148,SS, 2.0998901640703,
Line 1145, P(1), 33.641604003906,Line 1145, P(2), 3.3749478344726,SS,
2.1089151694397,
Line 1205, P(1), 33.35844543457,Line 1205, P(2),
3.375510335083,SS, 2.0643102946386,
Line 1145, P(1), 32.752617797852,Line
1145, P(2), 3.31717894104,SS, 2.0741481177949,
Line 1205, P(1),
32.909013519287,Line 1205, P(2), 3.3391938389587,SS, 2.0498251949762,
Line 1145, P(1), 32.322941131592,Line 1145, P(2), 3.3105906425476,SS,
2.0596161611429,
Line 1205, P(1), 32.581817207337,Line 1205, P(2),
3.3268205656814,SS, 2.0457892340368,
Line 1145, P(1),
32.445176734924,Line 1145, P(2), 3.3345338653946,SS, 2.0545053845769,
Line 1205, P(1), 32.793054323197,Line 1205, P(2), 3.3380288455677,SS,
2.0433446298064,
Line 1145, P(1), 32.983610162735,Line 1145, P(2),
3.3581154185581,SS, 2.043986136359,
Line 1205, P(1), 32.883161923885,Line
1205, P(2), 3.3502917053389,SS, 2.0416162615159,
Line 1145, P(1),
32.862480647564,Line 1145, P(2), 3.3591699984431,SS, 2.0465694470293,
Line 1205, P(1), 32.810410904288,Line 1205, P(2), 3.3433141337866,SS,
2.0413212917395,
Line 1145, P(1), 32.699622027278,Line 1145, P(2),
3.3399295671195,SS, 2.0414963743393,
Line 1205, P(1), 32.74550700143,Line
1205, P(2), 3.3425201016743,SS, 2.0410627037328,
Line 1145, P(1),
32.783544858843,Line 1145, P(2), 3.338927096789,SS, 2.0424366845585,
Line
1205, P(1), 32.775165999867,Line 1205, P(2), 3.3449121282012,SS,
2.040995561113,
Line 1145, P(1), 32.710262097009,Line 1145, P(2),
3.3441180960889,SS, 2.0421598297298,
Line 1205, P(1),
32.785373702468,Line 1205, P(2), 3.3435151243621,SS, 2.0409813928778,
Line 1145, P(1), 32.815032700906,Line 1145, P(2), 3.345907150889,SS,
2.0409980953179,
Line 1205, P(1), 32.797651276037,Line 1205, P(2),
3.3450603885853,SS, 2.0409441393877,
Line 1145, P(1),
32.807858978638,Line 1145, P(2), 3.3436633847463,SS, 2.0411941754316,
Line 1205, P(1), 32.78333924456,Line 1205, P(2), 3.3445999423374,SS,
2.0409374683013,
Line 998, P(1), 32.797651276037,Line 998, P(2),
3.3450603885853,SS, 2.0409441393877,
Third run.
Line 936, P(1), 53.95,Line 936,
P(2), 2.875535,SS, 102.22541693667,
Line 936, P(1), 0.005,Line 936, P(2),
5.75607,SS, 458.0822613329,
Line 936, P(1), 107.895,Line 936, P(2),
5.74607,SS, 61.783911986669,
Line 1145, P(1), 161.84,Line 1145, P(2),
2.865535,SS, 173.88334774957,
Line 1205, P(1), 121.38125,Line 1205, P(2),
3.58816875,SS, 116.98329000132,
Line 1145, P(1), 40.46375,Line 1145,
P(2), 5.03343625,SS, 35.92900828043,
Line 1328, P(1),
0.0049999999999955,Line 1328, P(2), 5.75607,SS, 458.0822613329,
Line
1145, P(1), 94.40875,Line 1145, P(2), 7.90397125,SS, 90.098930753045,
Line 1205, P(1), 84.2940625,Line 1205, P(2), 6.6468621875,SS,
59.196324322889,
Line 1145, P(1), 16.8628125,Line 1145, P(2),
5.9342284375,SS, 135.24858095577,
Line 1205, P(1), 85.136953125,Line
1205, P(2), 5.793109609375,SS, 45.599651570872,
Line 1145, P(1),
41.306640625,Line 1145, P(2), 4.179683671875,SS, 9.6629977626473,
Line
1328, P(1), 19.8129296875,Line 1328, P(2), 2.9460944140625,SS,
48.35125235276,
Line 1145, P(1), 3.3665625,Line 1145, P(2),
3.4200103125,SS, 1102.9762211153,
Line 1205, P(1), 63.01107421875,Line
1205, P(2), 5.1998347851562,SS, 27.835430420964,
Line 1145, P(1),
63.85396484375,Line 1145, P(2), 4.3460822070312,SS, 26.33624872968,
Line
1145, P(1), 42.14953125,Line 1145, P(2), 3.32593109375,SS, 17.393061276561,
Line 1145, P(1), 19.60220703125,Line 1145, P(2), 3.1595325585937,SS,
61.588765063108,
Line 1205, P(1), 52.791025390625,Line 1205, P(2),
4.0494447949219,SS, 16.188902608271,
Line 1145, P(1),
51.948134765625,Line 1145, P(2), 4.9031973730469,SS, 21.428871221242,
Line 1205, P(1), 44.599182128906,Line 1205, P(2), 3.7202476635742,SS,
9.7265980481916,
Line 1145, P(1), 33.114797363281,Line 1145, P(2),
3.8504865405273,SS, 10.662627236631,
Line 1205, P(1),
38.033854370117,Line 1205, P(2), 3.900226104126,SS, 6.0023362189518,
Line
1145, P(1), 34.741312866211,Line 1145, P(2), 4.3596621124268,SS,
24.243490159434,
Line 1205, P(1), 42.134714813232,Line 1205, P(2),
3.8801012757874,SS, 6.1726013063893,
Line 1145, P(1), 38.86192855835,Line
1145, P(2), 3.6006437080383,SS, 4.2444287485163,
Line 1328, P(1),
37.639572525024,Line 1328, P(2), 3.31112372612,SS, 7.676641736164,
Line
1145, P(1), 34.761068115234,Line 1145, P(2), 3.620768536377,SS,
3.4095522736531,
Line 1328, P(1), 31.074244766235,Line 1328, P(2),
3.4911021666718,SS, 5.1209078941407,
Line 1145, P(1),
35.589142303467,Line 1145, P(2), 3.3211861402893,SS, 4.1390273673492,
Line 1145, P(1), 31.488281860352,Line 1145, P(2), 3.3413109686279,SS,
2.4459738911925,
Line 1328, P(1), 27.801458511353,Line 1328, P(2),
3.2116445989227,SS, 6.2036721572724,
Line 1145, P(1),
30.660207672119,Line 1145, P(2), 3.6408933647156,SS, 9.9144605263245,
Line 1205, P(1), 34.35690864563,Line 1205, P(2), 3.4011129463959,SS,
2.2577901256675,
Line 1145, P(1), 31.084122390747,Line 1145, P(2),
3.1216553786469,SS, 3.1800806326377,
Line 1205, P(1),
32.003358821869,Line 1205, P(2), 3.2464336680794,SS, 2.2374603234028,
Line 1145, P(1), 34.871985607147,Line 1145, P(2), 3.3062356458473,SS,
3.5494405370174,
Line 1205, P(1), 32.33420779705,Line 1205, P(2),
3.3325421379328,SS, 2.0666876046599,
Line 1145, P(1),
29.980657973289,Line 1145, P(2), 3.1778628596163,SS, 2.7195546130517,
Line 1205, P(1), 33.262845977545,Line 1205, P(2), 3.345300424701,SS,
2.0926701000815,
Line 1145, P(1), 33.593694952726,Line 1145, P(2),
3.4314088945544,SS, 2.1639717441678,
Line 1205, P(1),
33.196110920012,Line 1205, P(2), 3.3851650879356,SS, 2.0670699306448,
Line 1145, P(1), 32.267472739518,Line 1145, P(2), 3.3724068011674,SS,
2.228833209146,
Line 1205, P(1), 33.014002668038,Line 1205, P(2),
3.3520770188176,SS, 2.0462423167393,
Line 1145, P(1),
32.152099545076,Line 1145, P(2), 3.2994540688147,SS, 2.0749256477923,
Line 1205, P(1), 32.935108076278,Line 1205, P(2), 3.3637373331554,SS,
2.0481203735751,
Line 1145, P(1), 33.614902947266,Line 1145, P(2),
3.3832722140402,SS, 2.0926620865005,
Line 1205, P(1),
32.654381584604,Line 1205, P(2), 3.3452246569596,SS, 2.0457161964489,
Line 1145, P(1), 32.733276176364,Line 1145, P(2), 3.3335643426218,SS,
2.044313243416,
Line 1328, P(1), 32.632360226407,Line 1328, P(2),
3.318477847355,SS, 2.0577742360983,
Line 1145, P(1), 32.37365509293,Line
1145, P(2), 3.3267119807639,SS, 2.0556246533607,
Line 1205, P(1),
32.853915774261,Line 1205, P(2), 3.3457357593042,SS, 2.0416352527934,
Line 1145, P(1), 32.932810366021,Line 1145, P(2), 3.3340754449663,SS,
2.0606137998114,
Line 1205, P(1), 32.723988779958,Line 1205, P(2),
3.3424373539613,SS, 2.0413347024539,
Line 1145, P(1),
32.844628377855,Line 1145, P(2), 3.3546087706437,SS, 2.0434247757671,
Line 1205, P(1), 32.816790327483,Line 1205, P(2), 3.3493476636382,SS,
2.0414673406547,
Line 1145, P(1), 32.68686333318,Line 1145, P(2),
3.3460492582953,SS, 2.0443252177227,
Line 1205, P(1),
32.812152663991,Line 1205, P(2), 3.345814134052,SS, 2.0409847870693,
Line
1145, P(1), 32.719351116467,Line 1145, P(2), 3.3389038243751,SS,
2.0414208068069,
Line 1205, P(1), 32.743710919221,Line 1205, P(2),
3.3415147841909,SS, 2.041083517343,
Line 1145, P(1), 32.831874803253,Line
1145, P(2), 3.3448915642815,SS, 2.0413465293014,
Line 1205, P(1),
32.750960285782,Line 1205, P(2), 3.3430509065414,SS, 2.0410419160616,
Line 1145, P(1), 32.819402030552,Line 1145, P(2), 3.3473502564025,SS,
2.0410540492313,
Line 1205, P(1), 32.800479252719,Line 1205, P(2),
3.3458913883496,SS, 2.0409628120575,
Line 1145, P(1),
32.861671630928,Line 1145, P(2), 3.3486546158602,SS, 2.0413494265221,
Line 1205, P(1), 32.778638122069,Line 1205, P(2), 3.3444518338711,SS,
2.0409448960776,
Line 1145, P(1), 32.766964710797,Line 1145, P(2),
3.3445290881687,SS, 2.041023841625,
Line 1205, P(1), 32.800855675692,Line
1205, P(2), 3.3454928725811,SS, 2.0409499026894,
Line 998, P(1),
32.778638122069,Line 998, P(2), 3.3444518338711,SS, 2.0409448960776,
Forth run settles on local minimum.
Line 936, P(1), 53.95,Line 936, P(2), 2.875535,SS, 102.22541693667,
Line
936, P(1), 107.895,Line 936, P(2), 5.74607,SS, 61.783911986669,
Line 936,
P(1), 107.895,Line 936, P(2), 5.74607,SS, 61.783911986669,
Line 1145,
P(1), 161.84,Line 1145, P(2), 8.616605,SS, 142.2776844524,
Line 1205,
P(1), 80.9225,Line 1205, P(2), 4.3108025,SS, 48.632072138638,
Line 1145,
P(1), 80.9225,Line 1145, P(2), 4.3108025,SS, 48.632072138638,
Line 1145,
P(1), 53.95,Line 1145, P(2), 2.875535,SS, 102.22541693667,
Line 1205,
P(1), 94.40875,Line 1205, P(2), 5.02843625,SS, 51.439958331528,
Line
1145, P(1), 67.43625,Line 1145, P(2), 3.59316875,SS, 59.790677271488,
Line 1205, P(1), 87.665625,Line 1205, P(2), 4.669619375,SS, 48.8243951096,
Line 1145, P(1), 74.179375,Line 1145, P(2), 3.951985625,SS, 51.788968057891,
Line 1205, P(1), 84.2940625,Line 1205, P(2), 4.4902109375,SS,
48.377389924662,
Line 1145, P(1), 84.2940625,Line 1145, P(2),
4.4902109375,SS, 48.377389924662,
Line 1145, P(1), 87.665625,Line 1145,
P(2), 4.669619375,SS, 48.8243951096,
Line 1205, P(1), 82.60828125,Line
1205, P(2), 4.40050671875,SS, 48.409772055128,
Line 1145, P(1),
85.97984375,Line 1145, P(2), 4.57991515625,SS, 48.520024962203,
Line
1205, P(1), 83.451171875,Line 1205, P(2), 4.445358828125,SS,
48.370812985992,
Line 1145, P(1), 83.451171875,Line 1145, P(2),
4.445358828125,SS, 48.370812985992,
Line 1328, P(1), 83.0297265625,Line
1328, P(2), 4.4229327734375,SS, 48.384483459713,
Line 1145, P(1),
82.60828125,Line 1145, P(2), 4.40050671875,SS, 48.409772055128,
Line
1205, P(1), 83.8726171875,Line 1205, P(2), 4.4677848828125,SS,
48.368524831584,
Line 1145, P(1), 83.8726171875,Line 1145, P(2),
4.4677848828125,SS, 48.368524831584,
Line 1145, P(1), 84.2940625,Line
1145, P(2), 4.4902109375,SS, 48.377389924662,
Line 1205, P(1),
83.66189453125,Line 1205, P(2), 4.4565718554688,SS, 48.368260591026,
Line
1145, P(1), 83.66189453125,Line 1145, P(2), 4.4565718554688,SS,
48.368260591026,
Line 998, P(1), 83.66189453125,Line 998, P(2),
4.4565718554688,SS, 48.368260591026,
Fifth run.
Line 936, P(1), 53.95,Line 936,
P(2), 2.875535,SS, 102.22541693667,
Line 936, P(1), 107.895,Line 936,
P(2), 0.005,SS, 827.76556655061,
Line 936, P(1), 0.005,Line 936, P(2),
0.005,SS, 794432555.95375,
Line 1145, P(1), 161.84,Line 1145, P(2),
2.875535,SS, 173.40316229394,
Line 1145, P(1), 107.895,Line 1145, P(2),
5.74607,SS, 61.783911986669,
Line 1328, P(1), 107.895,Line 1328, P(2),
8.616605,SS, 110.61390089695,
Line 1145, P(1), 0.0049999999999955,Line
1145, P(2), 5.74607,SS, 459.81413559632,
Line 1205, P(1), 121.38125,Line
1205, P(2), 3.59316875,SS, 116.7420797571,
Line 1145, P(1), 40.46375,Line
1145, P(2), 5.02843625,SS, 35.755824552843,
Line 1328, P(1),
0.0049999999999955,Line 1328, P(2), 5.74607,SS, 459.81413559632,
Line
1145, P(1), 94.40875,Line 1145, P(2), 7.89897125,SS, 89.97104688751,
Line
1205, P(1), 84.2940625,Line 1205, P(2), 6.6431121875,SS, 59.118073604101,
Line 1145, P(1), 16.8628125,Line 1145, P(2), 5.9254784375,SS,
135.22120289058,
Line 1205, P(1), 85.136953125,Line 1205, P(2),
5.790922109375,SS, 45.576204375136,
Line 1145, P(1), 41.306640625,Line
1145, P(2), 4.176246171875,SS, 9.5962006218278,
Line 1328, P(1),
19.8129296875,Line 1328, P(2), 2.9428131640625,SS, 48.192681762847,
Line
1145, P(1), 3.3665625,Line 1145, P(2), 3.4137603125,SS, 1106.3063869243,
Line 1205, P(1), 63.01107421875,Line 1205, P(2), 5.1966316601563,SS,
27.788541058577,
Line 1145, P(1), 63.85396484375,Line 1145, P(2),
4.3444415820312,SS, 26.358275679257,
Line 1145, P(1), 42.14953125,Line
1145, P(2), 3.32405609375,SS, 17.487215019387,
Line 1145, P(1),
19.60220703125,Line 1145, P(2), 3.1558606835938,SS, 61.407403898108,
Line
1205, P(1), 52.791025390625,Line 1205, P(2), 4.0472963574219,SS,
16.217144711547,
Line 1145, P(1), 51.948134765625,Line 1145, P(2),
4.8994864355469,SS, 21.352338525923,
Line 1205, P(1),
44.599182128906,Line 1205, P(2), 3.7179136791992,SS, 9.7652009442859,
Line 1145, P(1), 33.114797363281,Line 1145, P(2), 3.8468634936523,SS,
10.553854423258,
Line 1205, P(1), 38.033854370117,Line 1205, P(2),
3.8969717095947,SS, 5.9480621844013,
Line 1145, P(1),
34.741312866211,Line 1145, P(2), 4.3553042022705,SS, 24.084518280983,
Line 1205, P(1), 42.134714813232,Line 1205, P(2), 3.877261309967,SS,
6.1650157593993,
Line 1145, P(1), 38.86192855835,Line 1145, P(2),
3.5979868476868,SS, 4.2606121581495,
Line 1328, P(1),
37.639572525024,Line 1328, P(2), 3.3088571855927,SS, 7.7475049652724,
Line 1145, P(1), 34.761068115234,Line 1145, P(2), 3.6176972473145,SS,
3.3703718563721,
Line 1328, P(1), 31.074244766235,Line 1328, P(2),
3.4879152159882,SS, 5.0541324751304,
Line 1145, P(1),
35.589142303467,Line 1145, P(2), 3.3187123854065,SS, 4.1857116093167,
Line 1145, P(1), 31.488281860352,Line 1145, P(2), 3.3384227850342,SS,
2.4253157688978,
Line 1328, P(1), 27.801458511353,Line 1328, P(2),
3.2086407537079,SS, 6.1482545330374,
Line 1145, P(1),
30.660207672119,Line 1145, P(2), 3.6374076469421,SS, 9.8084127162756,
Line 1205, P(1), 34.35690864563,Line 1205, P(2), 3.3983862007904,SS,
2.2667480999134,
Line 1145, P(1), 31.084122390747,Line 1145, P(2),
3.1191117385101,SS, 3.2197411325413,
Line 1205, P(1),
32.003358821869,Line 1205, P(2), 3.2437581157112,SS, 2.253421261503,
Line
1145, P(1), 34.871985607147,Line 1145, P(2), 3.3037215314674,SS,
3.5911336268795,
Line 1205, P(1), 32.33420779705,Line 1205, P(2),
3.3297474716425,SS, 2.0630241133076,
Line 1145, P(1),
29.980657973289,Line 1145, P(2), 3.1751193865633,SS, 2.7198650155318,
Line 1205, P(1), 33.262845977545,Line 1205, P(2), 3.3425694972336,SS,
2.1004047855685,
Line 1145, P(1), 33.593694952726,Line 1145, P(2),
3.4285588531649,SS, 2.1535948271625,
Line 1205, P(1),
33.196110920012,Line 1205, P(2), 3.3823586688015,SS, 2.0628127545543,
Line 1145, P(1), 32.267472739518,Line 1145, P(2), 3.3695366432104,SS,
2.2129579824295,
Line 1205, P(1), 33.014002668038,Line 1205, P(2),
3.3493112837278,SS, 2.0481784108325,
Line 1145, P(1), 33.875905791,Line
1145, P(2), 3.4019224808868,SS, 2.1239128448318,
Line 1205, P(1),
32.719632295538,Line 1205, P(2), 3.3477912239536,SS, 2.0438060560288,
Line 1145, P(1), 32.537524043564,Line 1145, P(2), 3.3147438388799,SS,
2.0577025826836,
Line 1205, P(1), 32.702170762676,Line 1205, P(2),
3.3316475463603,SS, 2.0447263154863,
Line 1145, P(1),
32.407800390176,Line 1145, P(2), 3.3301274865861,SS, 2.0545736349787,
Line 1205, P(1), 32.862452098572,Line 1205, P(2), 3.3445153344424,SS,
2.0423395340364,
Line 1145, P(1), 32.879913631434,Line 1145, P(2),
3.3606590120356,SS, 2.0472805931821,
Line 1205, P(1),
32.746606479865,Line 1205, P(2), 3.3389004127791,SS, 2.0416145276112,
Line 1145, P(1), 32.8894262829,Line 1145, P(2), 3.3356245232679,SS,
2.0528946741859,
Line 1205, P(1), 32.762080792378,Line 1205, P(2),
3.3447495487822,SS, 2.0411085317482,
Line 1145, P(1),
32.646235173671,Line 1145, P(2), 3.3391346271189,SS, 2.0427550043218,
Line 1205, P(1), 32.808397867347,Line 1205, P(2), 3.3431701576115,SS,
2.041321895925,
Line 1145, P(1), 32.82387217986,Line 1145, P(2),
3.3490192936145,SS, 2.0413041123636,
Line 1145, P(1),
32.777555104891,Line 1145, P(2), 3.3505986847852,SS, 2.0431032615262,
Line 1205, P(1), 32.800687176733,Line 1205, P(2), 3.3450272894049,SS,
2.040954792028,
Line 1145, P(1), 32.738895789251,Line 1145, P(2),
3.3407575445726,SS, 2.0411539830207,
Line 1205, P(1),
32.760139886904,Line 1205, P(2), 3.342822981833,SS, 2.0409866588172,
Line
1145, P(1), 32.798746271258,Line 1145, P(2), 3.3431007224558,SS,
2.0411795202614,
Line 1205, P(1), 32.771247162098,Line 1205, P(2),
3.3443373422006,SS, 2.0409735435541,
Line 1145, P(1),
32.811794451928,Line 1145, P(2), 3.3465416497725,SS, 2.0409951790314,
Line 1205, P(1), 32.77305352816,Line 1205, P(2), 3.3437526488179,SS,
2.0409471195076,
Line 998, P(1), 32.800687176733,Line 998, P(2),
3.3450272894049,SS, 2.040954792028,
References:
Yamaoka K, Tanigawara Y, Nakagawa T, Uno T. A pharmacokinetic analysis
program (multi) for microcomputer. J Pharmacobiodyn. 1981 Nov;4(11):879-85.
doi: 10.1248/bpb1978.4.879. PMID: 7328489.
Yamaoka K, Nakagawa T,
Tanaka H, Yasuhara M, Okumura K, Hori R. A nonlinear multiple regression
program, MULTI2 (BAYES), based on Bayesian algorithm for microcomputers.
J Pharmacobiodyn. 1985 Apr;8(4):246-56. doi: 10.1248/bpb1978.8.246.
PMID: 3839848.