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·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.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Soons PA, Mulders TMT, Uchida E, et al. (1993) Stereoselective pharmacokinetics of oral felodipine and nitrendipine in healthy subjects: correlation with nifedipine pharmacokinetics. Eur J Clin Pharmacol 44:163–169
Soons PA, Cohen AF, Breimer DD (1993) Comparative effects of felodipine, nitrendipine and nifedipine in healthy subjects: concentration-effect relationships of racemic drugs and enantiomers. Eur J Clin Pharmacol 44:113–120
Takenaka T, Miyazaki I, Asano M, et al. (1982) Vasodilator and hypotensive effects of the optical isomers of nicardipine (YC-93), a new Ca2+ antagonist. Jpn J Pharmacol 32:665–670
Tokuma Y, Fujiwara T, Noguchi H (1987) Determination of (+)- and (-)-nilvadipine in human plasma using chiral stationary-phase liquid chromatography and gas chromatographymass spectrometry, and a preliminary pharmacokinetic study in humans. J Pharm Sci 76:310–313
Tokuma Y, Fujiwara T, Noguchi H (1987) Plasma levels of (+)- and (-)-nivaldipine after oral dosing with racemic (+-)-nivaldipine in man. Res Commun Clin Pathol Pharmacol 57:229–237
Okamoto Y, Aburatani R, Hatada K, et al. (1990) Optical resolution of dihydropyridine enantiomers by high-performance liquid chromatography using phenylcarbamates of polysaccharides as a chiral stationary phase. J Chromatogr 513:375–378
Higuchi S, Sasaki H, Shiobara Y et al. (1977) Absorption, excretion and metabolism of a new dihydropyridine diester cerebral vasodilator in rats and dogs. Xenobiotica 7:469–479
Niwa T, Tokuma Y, Nakagawa K et al. (1988) Stereoselective oxidation and plasma protein binding of nilvadipine, a new dihydropyridine calcium antagonist, in man. Res Commun Chem Pathol Pharmacol 60:161–172
Glossmann H, Ferry DR, Goll A, et al. (1985) Calcium channels and calcium channel drugs: recent biochemical and biophysical findings. Arzneimittelforschung/Drug Res 35:1917–1935
Brisac AM, Champeroux P, Lucet B, et al. (1988) Central and peripheral hypotensive effects of the optical isomers of nicardipine, a dihydropyridine calcium channel antagonist, in rats. Eur J Pharmacol 146:171–174
Aoki K, Sato K, Kawaguchi Y, et al. (1982) Acute and long-term hypotensive effects and plasma concentrations of nifedipine in patients with essential hypertension. Eur J Clin Pharmacol 23:197–201
Pedersen OL, Mikkelsen E (1979) Acute and chronic effects of nifedipine in essential hypertension. Eur J Clin Pharmacol 15:235–240
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Iwaoka, T., Inoue, J., Naomi, S. et al. Determination of (+)- and (-)-nicardipine concentrations in human serum and their correlation with the antihypertensive effect after oral administration of racemic nicardipine. Eur J Clin Pharmacol 48, 345–349 (1995). https://doi.org/10.1007/BF00194949
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00194949