title: Effects of morin on the pharmacokinetics of nicardipine after oral and intravenous administration of nicardipine in rats.
abstract: 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.
authors.affiliation: College of Pharmacy, Chosun University, 375 Su-suk Dong, Dong-Gu, Gwangju, Korea.
authors.forename: Yong-Ji
authors.initials: YJ
authors.lastname: Piao
authors.forename: Jun-Shik
authors.initials: JS
authors.lastname: Choi
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001682:Biological Availability; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D065692:Cytochrome P-450 CYP3A Inhibitors; D004347:Drug Interactions; D005419:Flavonoids / Q000494:pharmacology*; D007275:Injections, Intravenous; D008297:Male; D009529:Nicardipine / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D047309:Flavones
chemical_list: D000975:Antioxidants; D002121:Calcium Channel Blockers; D065692:Cytochrome P-450 CYP3A Inhibitors; D005419:Flavonoids; D009529:Nicardipine; C008548:morin; D047309:Flavones