흰쥐에서 에피가로카테친이 경구 및 정맥으로 투여된 니칼디핀의 약물동태에 미친 영향

Abstract

Epigallocatechin gallate (EGCG), a natural polyphenol compound found in fruits and red wine, has irreversible inhibition for cytochrome P450 (CYP) 3A and P-glycoprotein (P-gp) in vitro. This study was to investigate the effect of EGCG on the pharmacokinetics of nicardipine after orally or intravenously administered nicardipine in rats. Nicardipine was administered orally (12 mg/kg) or intravenously (i.v., 4 mg/kg) with or without oral administration of EGCG (0.6, 3 or 12 mg/kg) to rats. Compared with the control group (given nicardipine alone), the area under the plasma concentration？time curve (AUC) was significantly (3 mg/kg, P < 0.05; 12 mg/kg, P < 0.01) increased by 56.2？78.7%, and the peak concentration (Cmax) was significantly (3 mg/kg, P < 0.05; 12 mg/kg, P < 0.01) increased by 37.2？47.5% in the presence of EGCG after orally administration of nicardipine. EGCG significantly (P < 0.05, 3 or 12 mg/kg) decreased the total body clearance (CL/F) of nicardipine by 56.2？78.6%. Consequently, the relative bioavailability (R.B.) of nicardipine was increased by 1.19- to 1.79-fold, the absolute bioavailability (A.B.) of nicardipine in the presence of EGCG was 17.2？19.7%, which was significantly (3 mg/kg, P < 0.05; 12 mg/kg, P < 0.01) enhanced compared with that of the control group (11.0%). Compared to the i.v. control, EGCG did not significantly change pharmacokinetic parameters of i.v. administration nicardipine. The enhanced oral bioavailability of nicardipine suggested that intestinal-mediated CYP 3A4 metabolism and P-gp-mediated efflux of nicardipine are inhibited by EGCG. Based on these results, nicardipine dosage should be adjusted when given with EGCG or EGCG-containing dietary supplement.