Effects of morin on the pharmacokinetics of nicardipine after oral and intravenous administration of nicardipine in rats

• Published in: Journal of pharmacy and pharmacology Vol. 60; no. 5; p. 625
• Main Authors: Piao, Yong-Ji, Choi, Jun-Shik
• Format: Journal Article
• Language: English
• Published: England 01.05.2008
• Subjects: Administration, Oral; Animals; Antioxidants - pharmacology; Biological Availability; Calcium Channel Blockers - administration & dosage; Calcium Channel Blockers - blood; Calcium Channel Blockers - pharmacokinetics; Cytochrome P-450 CYP3A Inhibitors; Drug Interactions; Flavonoids - pharmacology; Injections, Intravenous; Male; Nicardipine - administration & dosage; Nicardipine - blood; Nicardipine - pharmacokinetics; Rats; Rats, Sprague-Dawley
• ISSN: 0022-3573
• DOI: 10.1211/jpp.60.5.0008

This study investigated the effects of orally administered morin, an inhibitor of cytochrome P450 3A (CYP3A) and P-glycoprotein (P-gp), on the pharmacokinetics of orally and intravenously administered nicardipine in rats. Nicardipine is reportedly a substrate for CYP3A4 and P-gp. Nicardipine was administered orally (12 mgkg(-1)) with or without orally administered morin (1.5, 7.5 and 15 mgkg(-1)), and intravenously (4 mgkg(-1)) with or without orally administered morin (7.5 and 15 mgkg(-1)). In the presence of morin, the pharmacokinetic parameters of nicardipine were significantly altered in the oral group but not in the intravenous group, suggesting that CYP3A-mediated metabolism of nicardipine in the liver is not significantly inhibited by morin. The presence of 7.5 and 15 mgkg(-1) of morin significantly increased (P < 0.01, 67.8-112%) the area under the plasma concentration-time curve and the peak plasma concentration (P < 0.01, 53.5-93.1%) of orally administered nicardipine. The presence of 7.5 and 15 mgkg(-1) of morin significantly decreased (P < 0.01, 40.4-52.8%) the total body clearance of orally administered nicardipine compared with the control group. The enhanced oral bioavailability of nicardipine suggests that intestinal-mediated CYP3A4 metabolism and P-gp-mediated efflux of nicardipine are inhibited by morin. Based on these results, concomitant use of morin or morin-containing dietary supplements with nicardipine may require close monitoring for potential drug interactions.