Altered pharmacokinetics of paclitaxel by the concomitant use of morin in rats.
The purpose of this study was to investigate the effect of morin on the pharmacokinetics of orally and intravenously administered paclitaxel in rats. Pharmacokinetic parameters of paclitaxel were determined in rats after an oral (30 mg kg(-1)) or intravenous (3 mg kg(-1)) administration of paclitaxel to rats in the presence and absence of morin (3.3 and 10 mg kg(-1)). Compared to the control given paclitaxel alone, pretreatment with morin 30 min prior to the oral administration of paclitaxel increased C(max) and AUC of paclitaxel by 70-90% and 30-70%, respectively, while there was no significant change in T(max) and terminal plasma half-life (T(1/2)) of paclitaxel. Consequently, absolute and relative bioavailability values of paclitaxel in the rats after the pretreatment with morin were significantly higher (p<0.05) than those from the control. In contrast, following an intravenous administration of paclitaxel (3.3 mg kg(-1)), the pharmacokinetic profiles of paclitaxel were not altered significantly in the presence of morin. Those results suggest that the enhanced oral exposure of paclitaxel should be mainly due to the inhibition effect of morin on the gastrointestinal extraction of paclitaxel during the intestinal absorption. Therefore, the concurrent use of morin or morin-containing dietary supplement may provide a therapeutic benefit in the oral delivery of paclitaxel.
Choi
Byung-Chul
BC
College of Pharmacy, Chung-ang University, Heukseok-dong, Dongjak-gu, Seoul, Republic of Korea.
Choi
Jun-Shik
JS
Han
Hyo-Kyung
HK
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors; D000284:Administration, Oral; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics; D000975:Antioxidants / Q000008:administration & dosage / Q000494:pharmacology; D019540:Area Under Curve; D001682:Biological Availability; D004347:Drug Interactions; D005419:Flavonoids / Q000008:administration & dosage / Q000494:pharmacology*; D007275:Injections, Intravenous; D008297:Male; D008657:Metabolic Clearance Rate / Q000187:drug effects; D017239:Paclitaxel / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D047309:Flavones
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000972:Antineoplastic Agents, Phytogenic; D000975:Antioxidants; D005419:Flavonoids; D017239:Paclitaxel; C008548:morin; D047309:Flavones