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Disposition Pathways and Pharmacokinetics of Herbal Medicines in Humans

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Abstract:

Pharmacokinetic studies have become an integral part of modern drug development, but these studies are not regulatory needs for herbal remedies. This paper updates our current knowledge on the disposition pathways and pharmacokinetic properties of commonly used herbal medicines in humans. To retrieve relevant data, the authors have searched through computer-based literatures by full text search in Medline (via Pubmed), ScienceDirect, Current Contents Connect (ISI), Cochrance Library, CINAHL (EBSCO), CrossRef Search and Embase (all from inception to May 2010). 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 Pglycoprotein (P-gp) 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. There are increasing pharmacokinetic studies of herbal remedies, but these studies are mainly focused on a small number of herbal remedies including St John's wort, milk thistle, sculcap, curcumin, echinacea, ginseng, ginkgo, and ginger. The pharmacokinetic data of a small number of purified herbal ingredients, including anthocyanins, berberine, catechins, curcumin, lutein and quercetin, are available. For the majority of herbal remedies used in folk medicines, data on their disposition and biological fate in humans are lacking or in paucity. For a herbal medicine, 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 an herbal remedy. In this regard, a safe and optimal use of herbal medicines requires a full understanding of their pharmacokinetic profiles. 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.





Keywords: Berberine; Catechins; Coptidis Rhizoma; Cortex Phellodendri; Curcuma longa; Curcumin; Echinacea angustifolia; Germander; Ginkgo biloba; Herbal medicine; Lycopene; Milk thistle; NADPH; P-glycoprotein; SULT; Silybin; Silybum marianum; St John's wort; Sulfotransferase; Tanshinone IIA; Teuchrium chamaedrys; Uridine Diphosphate Glucuronosyltransferase (UGT)-Mediated Conjugation; Zingiber officinale; a-nicotinamide adenine dinucleotide phosphate; absorption; alcohol/aldehyde dehydrogenease; amidase; arboxylesterase; baicalein 6-O-sulfate; caftaric acid; chlorogenic acid; cichoric acid; cynarin; cytochrome P450; echinacoside; epoxide hydrolase; flavincontaining monooxygenases; metabolism; monoamine oxidase; peroxidase; pharmacokinetics; terpenoids; toxicity; xenobiotics

Document Type: Research Article

DOI: http://dx.doi.org/10.2174/092986710793205336

Publication date: January 1, 2010

More about this publication?
  • Current Medicinal Chemistry covers all the latest and outstanding developments in medicinal chemistry and rational drug design. Each issue contains a series of timely in-depth reviews written by leaders in the field covering a range of the current topics in medicinal chemistry. Current Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments.
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