Renal excretion of unchanged PF-06282999 in preclinical species after i.v. administration
| Species | Renal Excretion | Total CLp | Total CLrenala | Unbound CLrenalb | Unbound CLrenal/GFR Ratioc |
|---|---|---|---|---|---|
| % of total dose | ml/min per kg | ||||
| Mouse | 44.2 | 10.1 | 4.03 | 9.8 | 1 |
| Rat | 30.5 | 41.8 | 11.6 | 28 | 3.2 |
| Dog | 26 | 3.39 | 0.96 | 1.9 | 0.5 |
| Monkey | 19.5 | 10.3 | 1.67 | 3.7 | 1.86 |
↵a Total CLrenal in blood was estimated by multiplying the total CLb with fraction of total i.v. dose of unchanged PF-06282999 excreted in urine. CLb was obtained by dividing CLp by the blood to plasma ratio in the individual animal species (mouse B/P = 1.1, rat B/P = 1.1, dog B/P = 0.91, monkey B/P = 1.2).
↵b Unbound CLrenal in blood was estimated by normalizing total CLrenal with the unbound free fraction in blood (mouse = 0.41, rat = 0.41, dog = 0.51, monkey = 0.45), which in turn was obtained by dividing the unbound plasma free fraction by the blood to plasma ratio.
↵c GFR values in rats, mice, dogs, and monkeys are 8.7, 10, 4, and 2 ml/min per kilogram, respectively.