Publication Cover
Xenobiotica
the fate of foreign compounds in biological systems
Volume 18, 1988 - Issue 1
48
Views
19
CrossRef citations to date
0
Altmetric
Research Article

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

, , &
Pages 21-28 | Received 12 Dec 1986, Published online: 22 Sep 2008
 

Abstract

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 species was 29–44%. The oral clearance in male rats was about 8 times higher than in female rats.

4. The free fraction of nilvadipine in plasma was 1·94% in mice, 1·89% in rabbits and 0·85% in dogs, with no dependence on plasma concentration over a range of 10–100ng/ml.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.