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Pharmacokinetics and Biliary Excretion of Fisetin in Rats

Huang, Miao-Chan, Hsueh, Thomas Y., Cheng, Yung-Yi, Lin, Lie-Chwen, Tsai, Tung-Hu
Journal of agricultural and food chemistry 2018 v.66 no.25 pp. 6300-6307
P-glycoproteins, bile, bile ducts, cannulas, excretion, males, metabolites, pharmacokinetics, polyethylene, rats, sulfates
The hypothesis of this study is that fisetin and phase II conjugated forms of fisetin may partly undergo biliary excretion. To investigate this hypothesis, male Sprague–Dawley rats were used for the experiment, and their bile ducts were cannulated with polyethylene tubes for bile sampling. The pharmacokinetic results demonstrated that the average area-under-the-curve (AUC) ratios (k (%) = AUCcₒₙⱼᵤgₐₜₑ/AUCfᵣₑₑ₋fₒᵣₘ) of fisetin, its glucuronides, and its sulfates were 1:6:21 in plasma and 1:4:75 in bile, respectively. Particularly, the sulfated metabolites were the main forms that underwent biliary excretion. The biliary excretion rate (kBE (%) = AUCbᵢₗₑ/AUCₚₗₐₛₘₐ) indicates the amount of fisetin eliminated by biliary excretion. The biliary excretion rates of fisetin, its glucuronide conjugates, and its sulfate conjugates were approximately 144, 109, and 823%, respectively, after fisetin administration (30 mg/kg, iv). Furthermore, biliary excretion of fisetin is mediated by P-glycoprotein.