Effects of licochalcone A on the bioavailability and pharmacokinetics of nifedipine in rats: possible role of intestinal CYP3A4 and P‐gp inhibition by licochalcone A

ABSTRACT The purpose of this study was to investigate the possible effects of licochalcone A (a herbal medicine) on the pharmacokinetics of nifedipine and its main metabolite, dehydronifedipine, in rats. The pharmacokinetic parameters of nifedipine and/or dehydronifedipine were determined after oral and intravenous administration of nifedipine to rats in the absence (control) and presence of licochalcone A (0.4, 2.0 and 10 mg/kg). The effect of licochalcone A on P‐glycoprotein (P‐gp) and cytochrome P450 (CYP) 3A4 activity was also evaluated. Nifedipine was mainly metabolized by CYP3A4. Licochalcone A inhibited CYP3A4 enzyme activity in a concentration‐dependent manner with a 50% inhibition concentration (IC 50 ) of 5.9 μ m . In addition, licochalcone A significantly enhanced the cellular accumulation of rhodamine‐123 in MCF‐7/ADR cells overexpressing P‐gp. The area under the plasma concentration–time curve from time 0 to infinity ( AUC ) and the peak plasma concentration ( C max ) of oral nifedipine were significantly greater and higher, respectively, with licochalcone A. The metabolite (dehydronifedipine)–parent AUC ratio ( MR ) in the presence of licochalcone A was significantly smaller compared with the control group. The above data could be due to an inhibition of intestinal CYP3A4 and P‐gp by licochalcone A. The AUC s of intravenous nifedipine were comparable without and with licochalcone A, suggesting that inhibition of hepatic CYP3A4 and P‐gp was almost negligible. Copyright © 2014 John Wiley & Sons, Ltd.