Table 2.
Summary of PF-04457845 pharmacokinetic parameters following single and multiple oral dosing (MRD study)
| PF-04457845 dose regimen | ||||
|---|---|---|---|---|
| Parameter* (Units) | 0.5 mg once daily | 1 mg once daily | 4 mg once daily | 8 mg once daily |
| Study day 1 | ||||
| N | 8 | 8 | 8 | 8 |
| AUC(0,τ) (ng ml−1 h) | 21.6 (25) | 68.3 (24) | 267 (28) | 724 (26) |
| Cmax,(ng ml−1) | 3.48 (56) | 10.6 (28) | 34.6 (42) | 92.8 (26) |
| tmax (h) | 1.00 (0.50, 2.00) | 1.00 (0.50, 1.02) | 1.00 (0.50, 2.00) | 1.00 (0.50, 1.00) |
| Study day 14 | ||||
| N, n | 8,7 | 8,8 | 7,7 | 8,8 |
| AUC(0,τ) (ng ml−1 h) | 65.5 (20) | 157 (27) | 585 (30) | 1420 (18) |
| Cmax (ng ml−1) | 6.93 (23) | 13.9 (29) | 53.7 (24) | 129 (17) |
| tmax (h) | 1.13 (0.50, 1.33) | 1.19 (0.53, 2.00) | 1.10 (1.08, 2.00) | 1.10 (0.50, 1.10) |
| Rac | 3.03 (20) | 2.30 (22) | 2.22 (12) | 1.96 (10) |
| t1/2 (h) | 18.5 (19) | 21.5 (21) | 20.0 (25) | 21.9 (25) |
| Ae (ng) | 0.000 (0) | 91.4 (141) | 3780 (70) | 3206 (57) |
| CLr (ml min−1) | ND | 0.0008 (5256) | 0.0869 (81) | 0.0341 (49) |
*
Geometric mean (%CV) for all except median (min, max) for tmax; arithmetic mean (%CV) for t1/2. Ae = amount excreted in the urine, AUC(0,τ) = area under the plasma concentration–time profile within the dosing interval of 0 to τ (24 h); CLr = renal clearance, Cmax = maximum observed concentration within the dosing interval, CV = coefficient of variation, N = number of subjects; n = number of subjects where t1/2 was determined, ND = not determined, Rac = accumulation ratio, t1/2 = terminal half-life, tmax = time to reach Cmax.