Effects of morin on the pharmacokinetics of nicardipine after oral and intravenous administration of nicardipine in rats.
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.
Piao
Yong-Ji
YJ
College of Pharmacy, Chosun University, 375 Su-suk Dong, Dong-Gu, Gwangju, Korea.
Choi
Jun-Shik
JS
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
D000975:Antioxidants; D002121:Calcium Channel Blockers; D065692:Cytochrome P-450 CYP3A Inhibitors; D005419:Flavonoids; D009529:Nicardipine; C008548:morin; D047309:Flavones