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영어

The aim of this study was to investigate the effect of fluvastatin on the pharmacokinetics of nicardipine in rats. Pharmacokinetic parameters of nicardipine were determined after an oral administration of nicardipine (12 mg/kg) to rats coadministered with fluvastatin (0.5 and 1.5 mg/kg). Compared with the control (given nicardipine alone), coadministration of fluvastatin (0.5 mg/kg) significantly (p<0.01) increased the area under the plasma concentration (AUC) and peak plasma concentration (Cmax) of nicardipine. The toral plasma clearance (CL/F) of nicardipine was decreased significantly (p<0.01, 0.5 mg/kg) compared to the control group. The relative bioavailability (RB%) of nicardipine increased from 1.23- to 1.68-fold. However there were no significant changes in tmax, Kel and t1/2 of nicardipine. The enhanced oral bioavailability of nicardipine suggests that intestinal-mediated CYP3A4 metabolism of nicardipine are competitively inhibited by fluvastatin. Based on these results, the concurrent use of fluvastatin significantly enhanced the oral exposure of nicardipine in rats.