Determination of (+)- and (-)-nicardipine concentrations in human serum and their correlation with the antihypertensive effect after oral administration of racemic nicardipine.

Abstract

Serum (+)- and (-)-nicardipine concentrations were determined after oral administration of racemic nicardipine, and the relationship between the concentration of each enantiomer and the percentage change in blood pressure was investigated. Serum concentrations of (+) and (-)-nicardipine were assayed separately by a method combining high-performance liquid chromatography (HPLC) with gas chromatography - mass spectrometry (GS-MS). Linear relationships were found with serum concentrations of 0.25-80 mg x ml(-1) for both enantiomers of nicardipine with correlation coefficients of greater than 0.999. A single oral dose of 40 mg racemic nicardipine was given to 15 patients with essential hypertension. Serum (+)-nicardipine concentration was 2-3 times higher than the concentration of (-)-nicardipine 1, 2, and 3 after drug administration. The logarithmically transformed value of the serum (+)-nicardipine concentration was inversely correlated with the percentage change in systolic blood pressure, the correlation being statistically significant 1 and 2 h after drug administration, and also inversely correlated with the percentage change in diastolic blood pressure 1, 2 and 3 h after drug administration. However, the logarithmically transformed value of serum (-)-nicardipine showed no significant correlations with the percentage change in either systolic or diastolic blood pressure.