ADME properties of herbal medicines in humans: Evidence, challenges andstrategies

Abstract

Herbal medicines, an important group of multicomponent therapeutics, are widely and increasignly used worldwide. Despite the popularitiy of herbal medicines, the clinical evidence that support the use of most herbal medicines is weak. Pharmacokinetic and absorption, distribution, metabolism and excretion (ADME) studies have been integrated into modern drug development, but ADMEstudies are generally not needed for herbal remedy discovery and development. For the majority of herbal medicines, data on their ADME and pharmacokinetic properties in humans are lacking or scant. An extensive literature search indicates that there are limited dataon ADME properties of herbal medicines in humans. Many herbal compounds undergo Phase I and/or Phase II metabolism in vivo, withcytochrome P450s (CYPs) and uridine diphosphate glucuronosyltransferases (UGTs) playing a major role. Some herbal ingredients aresubstrates of P-glycoprotein (P-gp/MDR1/ABCB1) which is highly expressed in the intestine, liver, brain and kidney. As such, theactivities of these drug metabolizing enzymes and drug transporters are critical determining factors for the in vivo ADME processes ofherbal remedies. There are increasing ADME studies of herbal remedies, but these studies are mainly focused on a small number ofherbal medicines including St John's wort, milk thistle, curcumin, echinacea, ginseng, ginkgo, and ginger. For an herbal medicine, thepharmacological activity is gained when the active agents or the active metabolites reach and sustain proper levels at their sites of action.Both the dose levels and ADME processes of active herbal components in the body govern their target-site concentrations and thus thetherapeutic responses. In this regard, a safe and optimal use of herbal medicines requires a full understanding of their ADME profiles. Tooptimize the use of herbal remedies, further studies to explore their ADME properties in humans are certainly warranted. © 2011 Bentham Science Publishers Ltd.