PK properties observed in in vivo studies with maribavir in cynomolgus monkeys and estimated from the semi-PBPK model. The fm(Gluc) was set as 0.728 unless specified otherwise. The twice-daily doses were administered 8 hours apart within each dosing day
| PK Properties on Maribavir in Plasma | Observed, Mean ± S.D. | Estimated/Predicted by Semi-PBPK Model |
|---|---|---|
| 13 mg/kg 14C-Maribavir Intravenous Bolus, Single Dose | ||
| AUC0–t (mg·h/l) | 17.4 ± 3.9 | 12.5 (fm(Gluc) = 0.728) 15.1 (fm(Gluc) = 0.853) |
| CL (l/h) | 2.99 ± 0.73 | 4.02 (fm(Gluc) = 0.728) 3.33 (fm(Gluc) = 0.853) |
| Vss (l) | 35.4 ± 6.5 | 35.2 (fm(Gluc) = 0.728) 45.8 (fm(Gluc) = 0.853) |
| 5 mg/kg Maribavir Intravenous Bolus, Single Dose | ||
| AUC0–t (mg·h/l) | 4.55 ± 0.71 | 5.05 |
| CL (l/h) | 4.47 ± 0.18 | 4.06 |
| Vss (l) | 36.8 ± 14.7 | 35.4 |
| 10 mg/kg Maribavir Oral Gavage, Single Dose | ||
| AUC0–t (mg·h/l) | 6.13 ± 3.6 | 6.21 |
| Cmax (mg/l) | 1.50 ± 1.0 | 1.01 |
| Tmax (h) | 2 ± 0 | 1.31 |
| F | 0.661 ± 0.33 | 0.615 |
| Fa | N/A | 0.671 |
| 10 mg/kg Twice-Daily Maribavir Oral Gavage, Multiple Dose | ||
| AUC (mg·h/l), day 2, 0–8 h | 3.60 ± 1.2 | 4.41 |
| Cmax (mg/l), day 2, 0–8 h | 0.97 ± 0.39 | 1.13 |
| AUC (mg·h/l), day 27, 0–8 h | 4.60 ± 0.33 | 4.83 |
| Cmax (mg/l), day 27, 0–8 h | 0.90 ± 0.05 | 1.20 |
| 30 mg/kg Twice-Daily Maribavir Oral Gavage, Multiple Dose | ||
| AUC (mg·h/l), day 2, 0–8 h | 8.70 ± 1.2 | 13.2 |
| Cmax (mg/l), day 2, 0–8 h | 2.55 ± 0.63 | 3.40 |
| AUC (mg·h/l), day 27, 0–8 h | 12.8 ± 1.4 | 14.5 |
| Cmax (mg/l), day 27, 0–8 h | 2.63 ± 0.38 | 3.59 |
| 90 mg/kg Twice-Daily Maribavir Oral Gavage, Multiple Dose | ||
| AUC (mg·h/l), day 2, 0–8 h | 32.1 ± 11 | 39.7 |
| Cmax (mg/l), day 2, 0–8 h | 7.3 ± 3.5 | 10.2 |
| AUC (mg·h/l), day 27, 0–8 h | 30.6 ± 3.2 | 43.5 |
| Cmax (mg/l), day 27, 0–8 h | 6.9 ± 1.1 | 10.8 |
AUC0–t, area under the conc.-time curve from time 0 to the last measurable time point; CL, clearance; F, bioavailability; Fa, fraction absorbed; N/A, not available; Tmax, time to peak conc.; Vss, volume of distribution at steady state.