Multiple-Dose Pharmacokinetics of Nilvadipine in Healthy Volunteers

Abstract

Nilvadipine, a new antihypertensive and antianginal drug, was studied in six healthy male volunteers to evaluate its steady‐state pharmacokinetics after oral dosing. The subjects were given a single dose of 4 mg, followed by 4 mg every 12 hours for six days after a washout period of more than 3 days. The pharmacokinetics of nilvadipine were well described by a linear model of triexponential equation with zero‐order absorption. The steady state was reached by the fourth day of multiple dosing, with a twofold accumulation of trough plasma concentration and no accumulation of peak concentration. The mean plasma concentration at steady state was 1.0 ng/mL. The optical enantiomers of nilvadipine were also determined in the plasma. The plasma concentration of (+)‐nilvadipine was about two and a half times higher than that of (‐)‐nilvadipine, and this ratio was unaffected by multiple dosing.