Pharmacokinetics of nilvadipine, a new dihydropyridine calcium antagonist, in mice, rats, rabbits and dogs.

1. The pharmacokinetics of nilvadipine in male and female rats, and in male mice, rabbits and dogs were studied after i.v. and oral dosing.2. After i.v. dosing (0·1 mg/kg), the plasma concentrations of nilvadipine declined two-or three- exponential with terminal half-lives of 0·73h in mice, 1·2h in male and female rats, 3·7h in rabbits and 5·0h in dogs. Sex difference in pharmacokinetics after i.v. dosing in rats was not found. The systemic plasma clearance was in the order of mice > rats > rabbits > dogs, and nearly equalled the hepatic blood flow in each species. The volume of distribution at steady-state was high (>4 L/kg) in all species.3. After oral dosing, plasma concentrations of nilvadipine peaked within 1 h in all species except for middle and higher doses (4 and 16 mg/kg) in dogs. The area under the plasma concentration-time curves in male rats (3·2-100 mg/kg) and dogs (1-16mg/kg) increased in proportion to the dose. Bioavailability was low in male rats (3–4%) and rabbits (2%), but in other spec...