Pharmacokinetic interaction between diltiazem and morin, a flavonoid, in rats.
The present study aims to investigate the effect of morin, a flavonoid, on the pharmacokinetics of diltiazem and its active metabolite, desacetyldiltiazem, in rats. Pharmacokinetic parameters of diltiazem and desacetyldiltiazem were determined in rats after an oral administration of diltiazem (15 mg kg(-1)) to rats in the presence and absence of morin (1.5, 7.5 and 15 mg kg(-1)). Compared to the control given diltiazem alone, the C(max) and AUC of diltiazem increased by 30-120% in the rats co-administered with a 1.5 or 7.5 mg kg(-1) of morin, while there was no significant change in T(max) and terminal plasma half-life (T(1/2)) of diltiazem in the presence of morin. Consequently, absolute and relative bioavailability values of diltiazem in the rats co-administered with morin were significantly higher (p<0.05) than those from the control group. Metabolite-parent AUC ratio in the presence of morin (7.5 mg kg(-1)) decreased by 30% compared to the control group, implying that coadministration of morin could be effective to inhibit the CYP3A4-mediated metabolism of diltiazem. In conclusion, the presence of morin significantly enhanced the oral exposure of diltiazem, suggesting that concurrent use of morin or morin-containing dietary supplement with diltiazem should require close monitoring for potential drug interactions.
College of Pharmacy, Chosun university, 375 Su-suk Dong, Dong-Gu, Gwangju, Republic of Korea.
Jun-Shik
JS
Choi
Hyo-Kyung
HK
Han
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors; D000818:Animals; D019540:Area Under Curve; D051544:Cytochrome P-450 CYP3A; D065607:Cytochrome P-450 Enzyme Inhibitors; D004110:Diltiazem / Q000493:pharmacokinetics*; D004347:Drug Interactions; D005419:Flavonoids / Q000494:pharmacology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D047309:Flavones
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D051544:Cytochrome P-450 CYP3A; D065607:Cytochrome P-450 Enzyme Inhibitors; D004110:Diltiazem; D005419:Flavonoids; C008548:morin; D047309:Flavones; C104464:CYP3A protein, human; C510163:CYP3A4 protein, human