TABLE 5

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.

SpeciesCmaxaTmaxaOral AUC0–∞aCLpVdsst1/2Oral Fb
ng/mlhng⋅h/mlml/min per kgl/kgh%
Mouse3650 ± 3251.0 ± 0.124,800 ± 101010.1 ± 0.830.90 ± 0.061.36 ± 0.12>100
Rat596 ± 2821.1 ± 0.881780 ± 28741.8 ± 9.652.13 ± 1.080.75 ± 0.1986
Dog4090 ± 9790.7 ± 0.311,800 ± 34803.39 ± 1.130.54 ± 0.042.2 ± 0.575
Monkey771 (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.