Table 3.
Summary of pharmacokinetic and logistic model parameter estimates
| Parameter description | Parametera | Unit | Value | Precision (%) |
|---|---|---|---|---|
| PK model | ||||
| Apparent oral clearance | TV(CL/F) | Liters/h | 3.42 | |
| Apparent vol of distribution | TV(V/F) | Liters | 29.2 | |
| Fast absorption rate constant | TV(ka, fast) | Liters/h | 3.56 | |
| Slow absorption rate constant | TV(ka, slow) | Liters/h | 1.25 | |
| Duration of zero-order absorption | TV(Dur) | h | 0.29 | |
| Proportion of fast absorbers | Pfast | 0.556 | ||
| Slope effect of covariate | θCL/F,WT | 0.0545 | ||
| Slope effect of covariate | θV/F,WT | 0.433 | ||
| Difference in V/F between males and females | θV/F,SEX | Liters | 4.55 | |
| Change in DUR following a fixed-dose combination | θDur,FDC | h | −0.0904 | |
| Stochastic model parameters | BSV(CL/F) | 0.0351 | ||
| BSV(V/F) | 0.0251 | |||
| BSV(Dur) | 0.957 | |||
| IOV(KA) | 0.623 | |||
| RES. ADD | mg/liter | 1.89 | ||
| RES. PROP | 0.0907 | |||
| PD model | ||||
| Probability of hepatotoxicity within 2 mo of comedication only | BASE | 0.0452 | 5 | |
| AUC at which 50% of the maximum probability (1) is reached | LAUCT50 | 8.4786 | 14 | |
| Exponent | EXPN | 3.45 | 7 |
a
TV, population-estimated typical value; θ, fixed-effect parameter; BSV, between-subject variability; IOV, interoccasion variability; RES. ADD, additive residual error; RES. PROP, proportional residual error.