PHARMACOKINETICS OF NICARDIPINE ENANTIOMERS IN HEALTHY-YOUNG VOLUNTEERS

Objectives: The present study was conducted to compare pharmacokinetic behaviors of nicardipine enantiomers given in different doses with di fferent formulations of racemic nicardipine in healthy volunteers. Met hods: One or two 20-mg racemic nicardipine tablets, and a 40-mg sustai ned-release capsule of nicardipine were administered to eight healthy volunteers in a cross-over fashion and pharmacokinetic parameters were evaluated. Enantiomer concentrations were determined by GC-MS combine d with chiral stationary phase HPLC. Results and conclusions: Serum co ncentration of (+)-nicardipine was approximately 7-3 times higher than that of (-)-nicardipine in 20- and 40-mg doses of conventional formul ations and a non-linear increase in bioavailability with dose was demo nstrated. The value for AUC of (+)-nicardipine was approximately 2.3-2 .8 times greater than that of the (-)-nicardipine (P < 0.05) when 20 a nd 40 mg racemic nicardipine were administered in a conventional prepa ration. Relative bioavailability of the sustained-release preparation vs the conventional preparation was 28% and 44% for (+)- and (-)-nicar dipinel respectively, for the 40-mg dose.