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.

Abstractglinide has affi nity for P-gp and it can signifi cantly contribute to potential drug-drug interactions with other P-gp substrates or inhibitors (Chang et al., 2006). Kajosaari et al. reported that co-administration of repaglinide with the known P-gp inhibitor cyclosporine A could signifi cantly increase the plasma concentrations of repaglinide in humans (Kajosaari et al., 2005).Nisoldipine is a calcium antagonist of the 1,4-dihydropyridine class, it is often clinically used as an anti-angina and vasodilating agent (Chandler et al., 1992). Nisoldipine is well absorbed from the gastrointestinal tract after oral administration, but undergoes rapid and extensive fi rst-pass metabolism in the gut wall and liver (van Harten et al., 1989). Nisoldipine is mainly eliminated by metabolism. Oxidation of 1,4-dihydropyridine (nisoldipine) to pyridine, catalysed by CYP3A4, is the major metabolic route (Guengerich et al., 1991). In general, the substrate and/or inhibitors of CYP3A4 and P-gp overlap with each other (Wacher et al., 1995), however, there are few reports about P-gp activity for nisoldipine. Therefore, we evaluated the P-gp activity of nisoldipine using rhodamine-123 retention assays in P-gp-overexpressing MCF-7/ADR cells. In order to verifi cation the inhibition of CYP enzyme activity, weOriginal Article