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Pharmacokinetics, tissue distribution and excretion study of trans-resveratrol-3-O-glucoside and its two metabolites in rats.

Phytomedicine 2019 March 14
BACKGROUND: Trans-resveratrol-3-O-glucoside (TRG), isolated from the Chinese traditional herbal medicine Huzhang, has been shown to have a wide range of pharmacological benefits.

PURPOSE: The aim of this study is to investigate the pharmacokinetics, tissue distribution and excretion of TRG and its metabolites, (TRN (trans-resveratrol-3-O-glucuronide) and TR (trans-resveratrol)), following a single intragastric (i.g.) administration of TRG in rats.

STUDY DESIGN: To evaluate the pharmacokinetic properties of TRG, TRN and TR, groups of rats were administrated a single i.g. dose of either 75, 150 or 300 mg/kg TRG. The absolute bioavailability of TRG was estimated from the ratios of AUC0-∞ values for oral and intravenous administration. Tissue distributions of TRG, TRN and TR in rats were investigated following a single i.g. administration to four groups at 150 mg/kg dosage of TRG. For urinary, fecal and biliary excretion study, TRG, TRN and TR excretions were recovered from a group of rats administered a single i.g. dose of 150 mg/kg TRG.

METHODS: The levels of TRG, TRN and TR in plasma, tissues, bile, urine and feces were measured by a rapid and sensitive LC-UV method. The precision was below 10.0%, and the accuracy was within ±9.9% for TRG, TRN and TR.

RESULTS: The concentrations of TRN were markedly higher than those of TRG and TR in plasma, urine and bile. TRG, TRN and TR showed linear dynamics in dose range of 75-300 mg/kg TRG. TRG had poor absolute bioavailability in rats. The major distribution tissues of TRG, TRN, and TR in rats were in the digestive tract. TRG, TRN and TR were all eliminated from tissues quickly. TRG was mostly excreted via the renal route in the form of TRN, which accounted for 52.8% of the administered dose up to 72 h.

CONCLUSION: Following a single i.g. administration to rats TRG was easily absorbed and rapidly converted to the metabolites TR and TRN. These metabolites were found to be mainly excreted by the kidneys.

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