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Pharmacokinetic mechanisms underlying the detoxification effect of Glycyrrhizae Radix et Rhizoma (Gancao): drug metabolizing enzymes, transporters, and beyond.
Expert Opinion on Drug Metabolism & Toxicology 2018 December 25
INTRODUCTION: Glycyrrhizae Radix et Rhizoma (Gancao in Chinese) is the most frequently used traditional Chinese medicine (TCM) owing to its various pharmacological effects and, more importantly, the synergistic effects that enhance the efficacy and reduce the toxicity of other TCMs. Areas covered: We reviewed publications, predominantly between 1990 and 2018, that examined pharmacokinetic interactions between Gancao and other TCMs, or the bioactive constituents of these TCMs. This review focuses on the underlying mechanisms and the components responsible for the pharmacokinetic modulation by Gancao. Expert opinion: In general, the pharmacokinetic effects of Gancao are a result of its constituents such as macromolecules, like proteins, and small molecules, such as saponins and flavonoids. The mechanisms are related to formation of complexes and the influence of these on drug solubility, permeability, distribution, and metabolism. The detoxification effect of a single dose of Gancao is mainly mediated by the suppression of the intestinal absorption of toxic constituents of the co-administered TCMs and is attributable to constituents that form complexes with the toxic compounds and cause them to sediment. In contrast, the detoxification effects of repeated doses of Gancao are mediated mainly via the induction of drug metabolizing enzymes and efflux transporters.
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