Effect of naringin pretreatment on bioavailability of verapamil in rabbits.
The aim of present study is to investigate the effect of naringin on the pharmacokinetics of verapamil and its major metabolite, norverapamil in rabbits. The pharmacokinetic parameters of verapamil and norverapamil were determined after administering verapamil (9 mg/kg) orally to rabbits in the pretreated with naringin (1.5, 7.5, and 15 mg/kg). Naringin pretreatment significantly altered the pharmacokinetic parameters of verapamil. Compared with the control group (given verapamil alone), the Ka, Cmax and AUC of verapamil were significantly (p<0.05 or p<0.01) increased in the pretreatment of naringin, However there were no significant change in Tmax and t1/2 of verapamil. Consequently, pretreatment of naringin significantly (p<0.05, p<0.01) increased the AB% of verapamil significantly in a dose dependent manner (p<0.05 or p<0.01), and elevated the RB% of verapamil by 1.26- to 1.69-fold. the MR of verapamil were significantly (p<0.05) increased in the pretreatment of naringin, implying that pretreatment of naringin may effectively inhibit the CYP3A4-mediated metabolism of verapamil. In conclusion, pretreatment of naringin enhanced the oral bioavailability of verapamil. Based on these results, the verapamil dosage should be adjusted when given with naringin or a naringin-containing dietary supplement.
College of Medicine, Chosun University, Gwangju 501-759, Korea.
Cheul-Ho
CH
Yeum
Jun-Shik
JS
Choi
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D019540:Area Under Curve; D001682:Biological Availability; D002121:Calcium Channel Blockers / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D044950:Flavanones / Q000494:pharmacology*; D006207:Half-Life; D007275:Injections, Intravenous; D008297:Male; D011817:Rabbits; D014700:Verapamil / Q000031:analogs & derivatives / Q000378:metabolism / Q000493:pharmacokinetics*
D000975:Antioxidants; D002121:Calcium Channel Blockers; D044950:Flavanones; C016904:norverapamil; D014700:Verapamil; C005274:naringin