Pharmacokinetics of Nicardipine following Intravenous and Oral Administration to the Same Human Subject

Abstract

The pharmacokinetic study of nicardipine in the same human after intravenous and oral adminstration was examined. The profile of nicardipine after bolus 1.05 mg injection fit well to a bi-exponential curve. Plasma nicardipine concentrations for constant rate infusion at 1.27 mg/hr for 3 hr declined from 3 to 7 hr with the same pattern as the bolus injection, but exhibited another slope after 7 hr that declined more gently. The γvalue was 0.0463 hr^-1, 1/5 the β-values. On the other hand, absolute bioavailability values for Perdipine LA® sustained-release capsule containing 40 mg nicardipine as hydrochloride salt after single and multiple doses were calculated by dividing AUCPO by AUCIV, correcting for administered dose. Bioavailability values calculated based on the bolus injection (about 20%) represented a 2-fold difference when compared to values derived from constant rate infusion data. Consequently, differences in bioavailability values must be considered carefully to calculate bioavailability accurately. When the γ-phase is detected as in the case of nicardipine disposition, we need to select the intravenous administration for detecting γ-phase.