Pharmacokinetics and Disposition of Plant Natural Products in Humans and the Clinical and Toxicological Implications

harmacokinetic studies have become an integral part of modern drug development, but these studies are not regulatory needs for herbal remedies. This paper highlights the pharmacokinetic properties and disposition pathways of commonly used plant natural products and the possible clinical and toxicological implications. For a plant natural product, the pharmacological effect is achieved when the bioactive agents or the metabolites reach and sustain proper levels at their sites of action. Both the dose levels and fates of active components in the body govern their target-site concentrations after administration of a herbal product. In this regard, a safe and optimal use of herbal products requires a full understanding of their pharmacokinetic profiles. Recently, there are increasing pharmacokinetic studies of herbal products, but these studies are mainly focused on a small number of herbal remedies including St John's wort, milk thistle, curcumin, echinacea, danshen, ginseng, ginkgo, and ginger. For the majority of herbal remedies used in folk medicines, data on their disposition and biological fate in humans are lacking or in paucity. Many herbal compounds undergo Phase I and/or Phase II metabolism in vivo, with cytochrome P450s (CYPs) and uridine diphosphate glucuronosyltransferases (UGTs) playing a major role. Some herbal ingredients are substrates of P-glycoprotein which is highly expressed in the intestine, liver, brain and kidney. As such, the activities of these drug metabolizing enzymes and drug transporters are determining factors for the in vivo bioavailability, disposition and distribution of herbal remedies. To optimize the use of herbal remedies, further clinical studies to explore their biological fate including the disposition pathways and kinetics in the human body are certainly needed.