Pharmacokinetics of Nilvadipine After Multiple Oral Dosing to Steady-State

Abstract

Forty-four healthy male volunteers were randomly assigned to receive one of four dosing regimens: placebo or a dose of 6, 8, 10 or 12 mg of nilvadipine administered at 0, 7 and 14 hr each day for 19 doses over seven days. There was a proportional relationship between the maximum plasma concentration of nilvadipine after the first dose and the last dose and the dose administered. There was also a proportional relationship between the area under the plasma concentration-time curve during the last dosing interval and the administered dose. Results showed that there was no accumulation of drug in plasma at steady-state. In addition, there was no dose-dependency in the oral clearance, elimination rate constant or terminal elimination half-life values. The pharmacokinetics of nilvadipine are linear upon multiple dosign over the dosing range studied