Table 2 Metabolic in vitro stability of LEO 134310 in mouse, rat, dog, minipig and human whole blood and hepatocytes and in vivo PK parameters in rat and dog. Predicted hepatic clearance (CLH) from hepatocytes (well stirred model). Mean values ± S.D.
Parameter | Rat | Dog | Minipig | Human |
|---|---|---|---|---|
In vitro (blood) half-life (min) | 2.2 (2.1, 2.2) (n = 2) | 3.3 ± 2.1 (n = 5) | 3.8 (n = 1) | 4.4 ± 2.2 (n = 4) |
In vitro (hepatocytes) CLH (mL/min/kg) | 57 (n = 1) | > 30 (n = 1) | > 35 (n = 1) | > 18 (n = 1) |
In vivo clearance (mL/min/kg) | 360 ± 85 (n = 3) | 470 ± 97 (n = 3) | – | – |
In vivo terminal half-life (min) | 190 ± 171 (n = 3) | 11 ± 1.2 (n = 3) | – | – |
