Effects of naringin on the pharmacokinetics of intravenous paclitaxel in rats.
It was reported that paclitaxel is an inhibitor of hepatic P-glycoprotein (P-gp) and hepatic microsomal cytochrome P450 (CYP) 3A1/2, and that naringin is an inhibitor of biliary P-gp and CYP3A1/2 in rats. The purpose of this study was to report the effects of oral naringin on the pharmacokinetics of intravenous paclitaxel in rats. Oral naringin (3.3 and 10 mg/kg) was pretreated 30 min before intravenous (3 mg/kg) administration of paclitaxel. After intravenous administration of paclitaxel, the AUC was significantly greater (40.8% and 49.1% for naringin doses of 3.3 and 10 mg/kg, respectively), and Cl was significantly slower (29.0% and 33.0% decrease, respectively) than controls. The significantly greater AUC could be due mainly to an inhibition of metabolism of paclitaxel via CYP3A1/2 by oral naringin. The inhibition of hepatic P-gp by oral naringin could also contribute to the significantly greater AUC of intravenous paclitaxel by oral naringin.
Lim
Sung-Cil
SC
College of Pharmacy, Chosun University, Gwangju, Republic of Korea.
Choi
Jun-Shik
JS
D000818:Animals; D019540:Area Under Curve; D001189:Aryl Hydrocarbon Hydroxylases / Q000037:antagonists & inhibitors / Q000502:physiology; D051544:Cytochrome P-450 CYP3A; D004347:Drug Interactions; D044950:Flavanones / Q000494:pharmacology*; D007262:Infusions, Intravenous; D008297:Male; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000502:physiology; D017239:Paclitaxel / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley
D044950:Flavanones; D008565:Membrane Proteins; D001189:Aryl Hydrocarbon Hydroxylases; C465260:Cyp3a2 protein, rat; C465138:Cyp3a23-3a1 protein, rat; D051544:Cytochrome P-450 CYP3A; C005274:naringin; D017239:Paclitaxel