Comparison between predicted and observed exposure for a 200-mg oral dose in human subjects
Compound Number | Prediction Method | Predicted AUCa | Observed AUCb | Observed/Predicted | |
|---|---|---|---|---|---|
| μM/h | |||||
| 1 | PBS (rat, dog, monkey, rabbit) | 10-15 | 17 ± 3 | 1.1-1.7 | |
| NAS (rat, dog, monkey, rabbit) | 14.6 ± 8.5 | 1.16 | |||
| NAS (rat, dog) | 15.5 ± 6.9 | 1.10 | |||
| 2 (Raltegravir) | PBS (rat, dog, monkey, rabbit) | 11-21 | 18 ± 4 | 0.9-1.6 | |
| NAS (rat, dog, monkey, rabbit) | 19.5 ± 2.8 | 0.92 | |||
| NAS (rat, dog) | 17.6 ± 1.1 | 1.02 | |||
| 3 | PBS (rat, dog, monkey, rabbit) | 16-34 | 10 ± 3 | 0.3-0.6 | |
| NAS (rat, dog, monkey, rabbit) | 15.5 ± 4.0 | 0.65 | |||
|
| NAS (rat, dog) | 11.5 ± 0.4 |
| 0.87 | |
↵ a Predicted AUC was calculated from the range of predicted human clearance values (see Table 3) and the estimated oral bioavailability, according to equation 7. S.E. values were calculated by propagation of the respective S.E. values.
↵ b AUC observed in healthy human volunteers ((Iwamoto et al., 2008; data on file, Merck Research Laboratories). Results are the mean ± S.D. (n = 6).