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Glucuronidation is the dominating in-vivo metabolism pathway of herbacetin:elucidation of herbacetin pharmacokinetics after intravenous and oral administration in rats

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中国药理学与毒理学杂志 2017年第10期31卷 1019-1019页

作者： Bei-kang GE Liang ZHAO Te QI Ping-xiang XU Ming XUE Department of Pharmacology School of Basic Medical SciencesCapital Medical University

OBJECTIVE To map a comprehensive metabolic pathway of herbacetin in rats,specifically,to elucidate the biotransformation of herbacetin in vivo and to simultaneously monitor the pharmacokinetic process of both parent drug and its major *** liquid chromatography/ion trap mass spectrometry(LC/MS n) and ultra-liquid chromatography coupled with mass spectrometry(UPLC/MS) were combined in the current study for qualitative and quantitative determinations of herbacetin and its metabolites in bile,urine and feces after both oral and intravenous administration of herbacetin to *** kinetic studies on the intestinal and hepatic metabolism of herbacetin were further conducted to elucidate metabolic profiles of herbacetin in rat tissues and ***,plasma concentration profiles of herbacetin and its metabolites in rats were obtained to characterize the overall pharmacokinetic behavior of *** It was found that herbacetin was excreted primarily from rat urine in the form of *** in vitro enzyme kinetic studies and in vivo pharmacokinetic investigations suggested an extensive hepatic metabolism of herbacetin and the high exposure of herbacetin-glucuronides in systemic *** clearance,half-life and bioavailability of herbacetin in rats were determined as(16.4±1.92)mL·kg^(-1)·min^(-1),(11.9±2.7)min,and 1.32%,*** basis of these findings,a comprehensive metabolic pathway of herbacetin in rats was *** addition,a physiology based pharmacokinetic(PBPK) model was successfully developed with the aid of the Gastro Plus to simulate the pharmacokinetic process of herbacetin in *** of the PBPK modeling can provide a useful starting point to understand and extrapolate pharmacokinetic parameters among different species,populations,and disease *** After oral administration,herbacetin was subjected to colonic degradation and extensive first pass metabolism,with g

关键词： herbacetin pharmacokinetics biotransformation glucuronidation hepatic metabolism colonic degradation

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