Effects of epigallocatechin gallate on the bioavailability and pharmacokinetics of diltiazem in rats

Abstract

This study investigated the effect of orally administered epigallocatechin gallate (EGCG), a flavonoid, on the bioavailability or pharmacokinetics of diltiazem and its main active metabolites desacetyldiltiazem in rats. Pharmacokinetic parameters of diltiazem and desacetyldiltiazem were determined following the oral administration of diltiazem (15 mg x kg(-1)) in the presence or absence of EGCG (1, 4 and 12 mg x kg(-1)). The area under the plasma concentration-time curve (AUC) and the peak concentration (Cmax) of diltiazem were significantly (P < 0.05, 4 mg x kg(-1) and P < 0.01, 12 mg x kg(-1)) increased in the presence of EGCG. The total body clearance (CL/F) was significantly (P < 0.05, 4 and 12 mg x kg(-1)) decreased in the presence of EGCG. Consequently, the absolute bioavailability (AB%) of diltiazem was significantly (P < 0.05, 4 mg x kg(-1) and P < 0.01, 12 mg x kg(-1)) increased compared with that of the control group. The relative bioavailability (RB%) of diltiazem was from 1.65- to 1.76-fold higher than that of the control group. The terminal half-life (t1/2) and time to reach the peak concentration (Tmax) of diltiazem did not change significantly in the presence of EGCG. EGCG significantly (P < 0.05, 12 mg x kg(-1)) increased the AUC and Cmax of desacetyldiltiazem. Metabolite-parent AUC ratio of desacetyldiltiazem was decreased, but did not change significantly. The presence of EGCG significantly enhanced the oral bioavailability of diltiazem due to inhibiting cytochrome P450 (CYP) 3A4-mediated metabolism and P-glycoprotein (P-gp) mediated efflux of diltiazem in the intestine.