Pharmacokinetic drug interactions by herbal drugs: Critical evaluation and clinical relevance

Pharmacokinetic herb-drug interactions are caused by an induction or inhibition of cytochrome P450 (CYP) enzymes or transporters e.g. P-glycoprotein. St. John. s wort extracts containing hyperforin increase the expression of CYP-enzymes and P-glycoprotein mainly in the gut and liver which leads to a clinically relevant decrease of the bioavailability of CYP and P-glycoprotein substrates. Contrarily, the bioactivation of the prodrug losartan is reduced by milk thistle extracts which is due to an inhibition of CYP2C9. However, the 15% reduction of the bioavailability of the active metabolite E-3174 is clinically not relevant. Also, minor changes in drug bioavailability observed in clinical studies for valerian, echinacea, ginkgo and hawthorne are clinically not relevant, although in vitro studies point to drug interactions in vivo. Since for herbal extracts a positive in vitro in vivo correlation regarding the impact on drug bioavailability is rare, results from in vitro studies should be carefully interpreted.