Preclinical pharmacokinetics of PF-06282999
All experiments involving animals were conducted in our AAALAC-accredited facilities and were reviewed and approved by the Pfizer Institutional Animal Care and Use Committee. Pharmacokinetic parameters were calculated from plasma concentration-time data and are reported as means ± S.D. for n = 3 and maximum values for n = 2. All pharmacokinetics were conducted in male sex of each species (Wistar rats, CD-1 mice, beagle dogs, and/or cynomolgus monkeys). Intravenous doses for PF-06282999 were 1 mg/kg and were administered as a solution. Oral doses for PF-06282999 were 3 or 5 mg/kg and were formulated in 5% HPMC in 20 mM Tris/0.5% HPMCAS.
| Species | Cmaxa | Tmaxa | Oral AUC0–∞a | CLp | Vdss | t1/2 | Oral Fb |
|---|---|---|---|---|---|---|---|
| ng/ml | h | ng⋅h/ml | ml/min per kg | l/kg | h | % | |
| Mouse | 3650 ± 325 | 1.0 ± 0.1 | 24,800 ± 1010 | 10.1 ± 0.83 | 0.90 ± 0.06 | 1.36 ± 0.12 | >100 |
| Rat | 596 ± 282 | 1.1 ± 0.88 | 1780 ± 287 | 41.8 ± 9.65 | 2.13 ± 1.08 | 0.75 ± 0.19 | 86 |
| Dog | 4090 ± 979 | 0.7 ± 0.3 | 11,800 ± 3480 | 3.39 ± 1.13 | 0.54 ± 0.04 | 2.2 ± 0.5 | 75 |
| Monkey | 771 (1040, 501) | 1.5 (1.0, 2.0) | 3720 (4130, 3300) | 10.3 (10.5,10.1) | 1.09 (1.17, 1.01) | 3.32 (5.22, 1.42) | 76 |
↵a Obtained from p.o. dose; HPMC, hydroxypropyl methylcellulose; HPMCAS = hydroxypropyl methylcellulose acetate succinate.