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

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 (IC₅₀) of 5.9 μm . 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 AUCs 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.