TABLE 5.
Pharmacokinetic parameters following single administration to male animals.
| Species | Route | Dose (mg/kg) | tmax (h) | Cmax (ng/ml) | AUCinf (ng.h/ml) | CL (L/h/kg) | Vz (L/kg) | T1/2,z (h) | Bioavail-ability (%) a |
|---|---|---|---|---|---|---|---|---|---|
| Rat | IV | 1 | 424 | 731 | 1.38 | 4.1 | 2.1 | ||
| Rat | PO | 3 | 4 | 73.6 | 573 | 26 | |||
| Dog | IV | 1 | 1,510 | 4,200 | 0.267 | 2.68 | 7.00 | ||
| Dog | PO | 30 | 2 | 6,920 | 131 000 | 108 b | |||
| Dog | PO | 100 | 7 | 6,320 | 258 000 | 62 b | |||
| Cyno | IV | 1 | 774 | 2,970 | 0.355 | 2.59 | 6.66 | ||
| Cyno | PO | 3 | 2 | 609 | 6,620 | 67 b | |||
| Cyno | PO | 10 | 6 | 1,250 | 20 000 | 68 b | |||
| Cyno | PO | 20 | 8 | 2,490 | 45 200 | 77 b | |||
| Cyno | PO | 100 | 6 | 3,640 | 107 000 | 36 b |
a
Bioavailability (%) = AUC (oral)/AUC (IV) * Dose (mg/kg) IV/Dose (mg/kg) oral.
b
I.v. and p.o. exposure values used for bioavailability calculation taken from different studies.
AUCinf: area under the plasma concentration-time curve from time zero to infinity; Cmax: maximum (peak) plasma drug concentration; CL: clearance; Cyno: cynomolgus monkey; tmax: time to reach maximum (peak) plasma concentration following oral drug administration; t1/2,z: terminal half-life; Vz: volume of distribution.