Pharmacokinetic parameters of PF02341066 and PF04217903 in preclinical species and humans after intravenous or oral administration
Data are expressed as means ± S.D. (n = 3 animals or 4 patients per group for PF02341066; n = 2 animals or 6 healthy volunteers per group for PF04217903).
| Compound | Species | Dosing Route | Dose | CLplasma | Vss | Cmax | tmax | AUC0–∞ | t1/2 | Foral |
|---|---|---|---|---|---|---|---|---|---|---|
| mg/kg | ml per min/kg | l/kg | μg/ml | h | μg · h/ml | h | % | |||
| PF02341066 | Rat | i.v. | 5 | 29 ± 8 | 13 ± 4 | —a | — | 3.0 ± 0.9 | 7.7 ± 1.8 | — |
| p.o. | 25 | — | — | 0.53 ± 0.10 | 4.7 ± 1.2 | 5.6 ± 0.8 | 7.0 ± 0.4 | 63 | ||
| Dog | i.v. | 5 | 9.0 ± 0.8 | 13 ± 2 | — | — | 9.3 ± 0.8 | 17 ± 4 | — | |
| p.o. | 25 | — | — | 0.62 ± 0.37 | 4.0 ± 2.0 | 12 ± 8 | 12 ± 3 | 65 | ||
| Monkey | i.v. | 5 | 34 ± 4 | 13 ± 1 | — | — | 2.5 ± 0.3 | 5.5 ± 0.2 | — | |
| p.o. | 25 | — | — | 0.24 ± 0.11 | 6 ± 0 | 4.1 ± 1.7 | 12 ± 3 | 42 | ||
| Human | p.o. | 100b | — | — | 0.061 ± 0.034 | 2.5 ± 1.7 | 0.60 ± 0.22 | 10 ± 2 | — | |
| PF04217903 | Rat | i.v. | 2.5 | 8.2 ± 0.5 | 1.6 ± 0.1 | — | — | 5.1 ± 0.3 | 3.7 ± 0.0 | — |
| p.o. | 10 | — | — | 2.7 ± 0.2 | 0.8 ± 0.4 | 15 ± 2 | 3.6 ± 0.2 | 71 | ||
| Dog | i.v. | 2.5 | 12 ± 2 | 3.7 ± 0.7 | — | — | 3.4 ± 0.6 | 5.2 ± 0.3 | — | |
| p.o. | 10 | — | — | 2.4 ± 0.8 | 2 ± 0 | 22 ± 1 | 5.1 ± 2.1 | 100 | ||
| Human | p.o. | 30b | — | — | 0.24 ± 0.14 | 1.2 ± 0.7 | 0.81 ± 0.20 | 6.6 ± 1.3 | — |