Effects of morin on the pharmacokinetics of etoposide in rats.
This study investigated the effects of orally administered morin, an inhibitor of CYP isozyme and P-glycoprotein (P-gp), on the pharmacokinetics of intravenous and orally administered etoposide in rats. It was reported that etoposide is a substrate for P-gp and metabolized mainly via CYP3A4 and to a lesser degree via CYP1A2 and 2E1. Etoposide was administered through intravenous (2 mg/kg) or oral (6 mg/kg) routes to rats with or without orally administered morin (5 or 15 mg/kg), which was administered 30 min before etoposide. The pharmacokinetic parameters of etoposide intravenously administered were not significantly different from other groups, suggesting that CYP 3A-mediated metabolism and the P-gp mediated efflux of etoposide in the liver and kidney seemed not to be markedly inhibited by orally administered morin. However, orally administered morin (15 mg/kg) significantly increased the AUC (45.8%), C(max) (32.0%) and the absolute bioavailability (35.9%) of orally administered etoposide compared with the control, which could be mainly due to inhibition of CYP isoenzyme and P-gp in the intestine by morin. The dosage regimen of etoposide should be taken into consideration for toxic reactions when combined with morin or dietary supplements containing morin in patients.
Li
Xiuguo
X
College of Pharmacy, Chosun University, Gwangju, Republic of Korea.
Yun
Jae-Kyung
JK
Choi
Jun-Shik
JS
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors; D000284:Administration, Oral; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000975:Antioxidants / Q000008:administration & dosage / Q000494:pharmacology*; D019540:Area Under Curve; D001682:Biological Availability; D003577:Cytochrome P-450 Enzyme System / Q000187:drug effects; D004347:Drug Interactions; D005047:Etoposide / Q000008:administration & dosage / Q000493:pharmacokinetics*; D005419:Flavonoids / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D007275:Injections, Intravenous; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D047309:Flavones
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000972:Antineoplastic Agents, Phytogenic; D000975:Antioxidants; D003577:Cytochrome P-450 Enzyme System; D005047:Etoposide; D005419:Flavonoids; C008548:morin; D047309:Flavones