```
** FINAL OUTPUT FROM Boomer (v2.7.7) **      22-Apr-1999 ---  2:55:15 pm

Title:  Fit to two lines simultaneously
Input: From Ch9905b.BAT
Output:  To Ch9905b.OUT
Data for [Drug] came from Ch9905bp.DAT
Data for Drug in Urine came from Ch9905bu.DAT
Fitting algorithm: Simplex Method
Weighting for [Drug]          by 1/a*Cp(Obs )^b
With a = 0.2500E-02 and b =  2.000
Weighting for Drug in Urine   by 1/a*Cp(Obs )^b
With a =  25.00     and b = 0.0000
Numerical integration method: 2) Fehlberg RKF45
with  2 de(s)
With relative error   0.1000E-03
With absolute error   0.1000E-03
PC =   0.1000E-04

** FINAL PARAMETER VALUES ***

#  Name                  Value       S.D.       C.V. %  Lower <-Limit-> Upper

1) ke                    0.14030                           0.00       10.
2) km                    0.68670E-01                       0.00       10.
3) V                      25.044                           0.10      0.10E+03

AIC =   -1.28234     Final WSS =   0.594421
R-squared =    1.000     Correlation Coeff =    1.000

** FINAL OUTPUT FROM Boomer (v2.7.7) **      22-Apr-1999 ---  2:55:15 pm

Title:  Fit to two lines simultaneously
Input: From Ch9905b.BAT
Output:  To Ch9905b.OUT
Data for [Drug] came from Ch9905bp.DAT
Data for Drug in Urine came from Ch9905bu.DAT
Fitting algorithm: DAMPING-GAUSS/SIMPLEX
Weighting for [Drug]          by 1/a*Cp(Obs )^b
With a = 0.2500E-02 and b =  2.000
Weighting for Drug in Urine   by 1/a*Cp(Obs )^b
With a =  25.00     and b = 0.0000
Numerical integration method: 2) Fehlberg RKF45
with  2 de(s)
With relative error   0.1000E-03
With absolute error   0.1000E-03
DT =   0.1000E-02     PC =   0.1000E-04 Loops =     1
Damping =     1

** FINAL PARAMETER VALUES ***

#  Name                  Value       S.D.       C.V. %  Lower <-Limit-> Upper

1) ke                    0.14030      0.465E-03  0.33      0.00       10.
2) km                    0.68667E-01  0.627E-03  0.91      0.00       10.
3) V                      25.045      0.159      0.63      0.10      0.10E+03

AIC =   -1.28234     Final WSS =   0.594421
R-squared =    1.000     Correlation Coeff =    1.000

Model and Parameter Definition

#  Name                    Value       Type From To     Dep  Start Stop

1) Dose                =   600.0        1    0    1       0    0    0
2) ke                  =  0.1403        2    1    2       0    0    0
3) km                  =  0.6867E-01    2    1    0       0    0    0
4) V                   =   25.04       18    1    1       0    0    0
5) ONE                 =   1.000       18    2    2       0    0    0

Data for [Drug]          :-

DATA #   Time       Calculated     Observed      (Weight)   Weighted residual

1   0.5000       21.5802       21.5000      0.930233     -0.746492E-01
2    1.000       19.4393       19.4000       1.03093     -0.405125E-01
3    2.000       15.7735       15.8000       1.26582      0.335150E-01
4    3.000       12.7990       12.7000       1.57480     -0.155946
5    6.000       6.83786       6.84000       2.92398      0.624350E-02
6    9.000       3.65312       3.70000       5.40541      0.253394
7    12.00       1.95168       1.95000       10.2564     -0.171955E-01

WSS for data set  1 =   0.9720E-01
R-squared =   0.9997     Correlation Coeff =    1.000

Data for Drug in Urine   :-

DATA #   Time       Calculated     Observed      (Weight)   Weighted residual

1   0.5000       39.9647       41.5000      0.200000      0.307053
2    1.000       75.9646       76.6000      0.200000      0.127077
3    2.000       137.604       140.500      0.200000      0.579160
4    3.000       187.620       187.000      0.200000     -0.124014
5    6.000       287.856       287.000      0.200000     -0.171271
6    9.000       341.407       341.000      0.200000     -0.814941E-01
7    12.00       370.017       370.000      0.200000     -0.341797E-02

WSS for data set  2 =   0.4972
R-squared =    1.000     Correlation Coeff =    1.000

Maximum value for [Drug]          is      21.500     at      0.5000

Calculation of AUC and AUMC based on trapezoidal rule

AUC and AUMC for [Drug]          using Observed data

Time         Concentration      AUC             AUMC

0.500000         21.5000
** Note that first time point is not zero **
1.00000         19.4000         10.2250         7.53750
2.00000         15.8000         27.8250         33.0375
3.00000         12.7000         42.0750         67.8875
6.00000         6.84000         71.3850         186.598
9.00000         3.70000         87.1950         298.107
12.0000         1.95000         95.6700         383.157
105.002         539.795

MRT =      5.1408

Calculation of AUC and AUMC using Method 9 of R.D. Purves

AUC and AUMC for [Drug]          using Observed data

Time         Concentration      AUC             AUMC

0.500000         21.5000
** Note that first time point is not zero **
1.00000         19.4000         10.2160         7.61827
2.00000         15.8000         27.7545         33.6262
3.00000         12.7000         41.9481         68.8521
6.00000         6.84000         70.3573         192.326
9.00000         3.70000         85.6879         304.966
12.0000         1.95000         93.8846         389.727
103.216         546.365

MRT =      5.2934

Plots of observed (*) and calculated values (+)
versus time for [Drug]         . Superimposed points (X)

21.58      Linear                      21.58      Semi-log
| +                                     | +
| *                                     | *
|                                       |   X
|                                       |
|   X                                   |      X
|                                       |
|                                       |
|                                       |         X
|                                       |
|      X                                |
|                                       |
|                                       |
|                                       |
|                                       |
|         X                             |
|                                       |                  X
|                                       |
|                                       |
|                                       |
|                                       |
|                                       |
|                                       |
|                                       |
|                  X                    |                           X
|                                       |
|                                       |
|                                       |
|                                       |
|                           X           |
|                                       |
|                                    X  |                                    X
|_____________________________________  |_____________________________________
1.950                                  1.950
0              <-->             12.     0              <-->             12.
Plot of Std Wtd Residuals (X)         Plot of Std Wtd  Residuals (X)
versus time for [Drug]                versus calcd Cp(i) for [Drug]

1.090                                  1.090
|                          X            |   X
|                                       |
|                                       |
|                                       |
|                                       |
|                                       |
|                                       |
|                                       |
|                                       |
|    X                                  |                         X
0=================X===================  0========X============================
|                                    X  |X
| X                                     |                                X
|X                                      |                                    X
|                                       |
|                                       |
|       X                               |                   X
|                                       |
-0.6708                                -0.6708
0.50       <-->             12.          2.0       <-->             22.
Plots of observed (*) and calculated values (+)
versus time for Drug in Urine  . Superimposed points (X)

370.0      Linear                      370.0      Semi-log
|                                    +  |                                    +
|                                    *  |                                    *
|                                       |                           X
|                           X           |
|                                       |                  X
|                                       |
|                                       |
|                                       |
|                  X                    |
|                                       |
|                                       |         X
|                                       |
|                                       |
|                                       |
|                                       |      X
|                                       |
|                                       |
|         X                             |
|                                       |
|                                       |
|                                       |
|      *                                |
|      +                                |   X
|                                       |
|                                       |
|                                       |
|                                       |
|   X                                   |
|                                       |
|                                       |
| X                                     | X
|_____________________________________  |_____________________________________
39.96                                  39.96
0              <-->             12.     0              <-->             12.
Plot of Std Wtd Residuals (X)         Plot of Std Wtd  Residuals (X)
versus time for Drug in Urine         versus calcd Cp(i) for Drug in Urine

2.491                                  2.491
|    X                                  |          X
|                                       |
|                                       |
|                                       |
|                                       |
|                                       |
|X                                      |X
|                                       |
|                                       |
|                                       |
| X                                     |   X
|                                       |
|                                       |
0====================================X  0====================================X
|                                       |
|       X                  X            |                X               X
|                 X                     |                           X
|                                       |
-0.7368                                -0.7368
0.50       <-->             12.          40.       <-->            0.37E+03
Plot of Std Wtd Residuals (X)        Plot of Std Wtd  Residuals (X)
versus time for all data              versus calcd Cp(i) for all data

2.491                                  2.491
|    X                                  |             X
|                                       |
|                                       |
|                                       |
|                                       |
|                                       |
|X                                      |   X
|                          X            |X
|                                       |
|                                       |
| X                                     |       X
|                                       |
|    X                                  | X
0=================X==================X  0X===================================X
|XX                                     | X
|       X                  X            |                  X              X
|       X         X                     | X                         X
|                                       |
-0.7368                                -0.7368
0.50       <-->             12.          2.0       <-->            0.37E+03
```