Pharmacokinetics and dose-dependency of LB30870 in rats, dogs, and monkeys

This study was to examine the pharmacokinetics of LB30870, a thrombin inhibitor, after IV and oral administration to rats, dogs, and monkeys. In rats and dogs, LB30870 showed linear pharmacokinetics after IV and oral administration. The oral bioavailability (BA) in rats was about 30 % with high inter-subject variability in the time to reach peak plasma concentration (T_max). Oral absorption of a solution and prototype tablet formulations of LB30870 were tested in dogs. T_max was 30 min and the BA values were 40.8–43.1 % with solution formulation. BA values after oral administration of the two tablet formulations at the dose of 100 mg/dog were 27.0 and 30.8 %. T_max were 60 min in the tablet formulation, indicating that the disintegration and dissolution of tablets caused delay in T_max compared to solution formulation. After IV administration of LB30870 to monkeys, the plasma concentrations decreased bi-exponentially and BA was 15.0 % after oral (20 mg/kg) dosing. In summary, linear pharmacokinetics of LB30870 were observed in both rats and dogs. The differences in BA among species could be due to difference in absorbed fraction and/or the first pass extraction (pre-systemic elimination) of LB30870.