DETERMINATION OF (-NICARDIPINE AND (-)-NICARDIPINE CONCENTRATIONS IN HUMAN SERUM AND THEIR CORRELATION WITH THE ANTIHYPERTENSIVE EFFECT AFTER ORAL-ADMINISTRATION OF RACEMIC NICARDIPINE())

Serum (+)- and (-)-nicardipine concentrations were determined after or al administration of racemic nicardipine, and the relationship between the concentration of each enantiomer and the percentage change in blo od pressure was investigated, Serum concentrations of (+)-and (-)-nica rdipine were assayed separately by a method combining high-performance liquid chromatography (HPLC) with gas chromatography - mass spectrome try (GS-MS). Linear relationships were found with serum concentrations of 0.25-80 mg . ml(-1) for both enantiomers of nicardipine with corre lation coefficients of greater than 0.999, A single oral dose of 40 mg racemic nicardipine was given to 15 patients with essential hypertens ion. Serum (+)-nicardipine concentration was 2-3 times higher than the concentration of (-)-nicardipine 1, 2, and 3 after drug administratio n, The logarithmically transformed value of the serum (+)-nicardipine concentration was inversely correlated with the percentage change in s ystolic blood pressure, the correlation being statistically significan t 1 and 2 h after drug administration, and also inversely correlated w ith the percentage change in diastolic blood pressure 1, 2 and 3 h aft er 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.