Enhanced Bioavailability of Verapamil after Oral Administration with Hesperidin in Rats

다국어 초록 (Multilingual Abstract)

The aim of this study was to investigate the effects of hesperidin on the pharmacokinetics of
verapamil and its major metabolite, norverapamil, in rats. The pharmacokinetic parameters of
verapamil and norverapamil in rats were measured after the oral administration of verapamil (9
mg/kg) in the presence or absence of hesperidin (3 or 10 mg/kg). Compared to the control
group, the presence of hesperidin significantly (p<0.01) increased the area under the plasma
concentration-time curve (AUC) of verapamil by 71.1–96.8% and the peak concentration (Cmax)
of verapamil by 98.3-105.2%. Hesperidin significantly (p<0.01) decreased the total plasma
clearance (CL/F) of verapamil by 41.6-49.2% in rats. However there was no significant change
in the time to reach the peak plasma concentration (Tmax), the elimination rate constant (Kel)
and the terminal half-life (T1/2) of verapamil in the presence of hesperidin. The AUC and Cmax of
norverapamil were significantly (p<0.05) higher in rats coadministrated with hesperidin than
those of the control. Consequently hesperidin significantly enhanced bioavailability of verapamil
in rats. These results might be due to the decreased efflux and metabolism of verapamil
in the intestine. Drug interactions should be concerned in the clinical setting when verapamil is
used concomitantly with hesperidin or hesperidin-containing dietary

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