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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

Author:
Ge, Beikang, Zhao, Liang, Li, Xiaorong, Xu, Pingxiang, Xue, Ming
Source:
Journal of functional foods 2018 v.40 pp. 659-669
ISSN:
1756-4646
Subject:
bile, bioavailability, biochemical pathways, enzyme kinetics, feces, humans, intravenous injection, oral administration, pharmacokinetics, rats, therapeutics, urine
Abstract:
The promising potential benefits of herbacetin in human entail its pharmacokinetic investigations, but the metabolic fate of this natural compound in vivo remains a field of unknown so far. The current study, for the first time, identified and quantified seven herbacetin-metabolites from rat urine, feces and bile after administration of herbacetin to rats. It was found that herbacetin was excreted primarily from rat urine in the form of glucuronide-conjugations. Subsequent 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 circulation. The clearance, t1/2 and bioavailability of herbacetin in rats were determined as 16.4 ± 1.92 ml·kg/min, 11.9 ± 2.7 min, and 1.32%, respectively. On basis of these findings, a comprehensive metabolic pathway of herbacetin in rats was composed, which was crucial for the further assessments of herbacetin therapeutic effects and mechanism of pharmacological action.
Agid:
5938017