Abstract
Gnaphalium affine is traditionally used to treat hyperuricemia and gout in China. Recently, the hypouricemic and renal protective effects of G. affine extract (GAD) have been deeply evaluated. However, little is known about the pharmacokinetics (PKs) of bioactive constituents in GAD. This study was aimed to investigate the individual and holistic pharmacokinetics of ten bioactive components (including caffeic acid, caffeoylquinic acids, and flavonoids) in rats after single and multiple administration of GAD. GAD was orally dosed to normal male rats at doses of 225, 450 or 900 mg/kg/day for 10 consecutive days and also orally administrated to uric acid nephropathy (UAN) rats at a dose of 900 mg/kg/day for 28 consecutive days. Integrated PKs of multiple components were calculated by area under the curve (AUC)-based weighting approach. All the components showed a double-peak phenomenon in terms of their plasma concentration-time curves suggesting that the components undergo enterohepatic circulation. The integrated AUC increased in a good dose-proportional manner with GAD dose. Compared with that in normal rats, the plasma exposure of caffeic acid and caffeoylquinic acids increased by 2.3- to 4.3-fold after 10-day chronic treatment of 900 mg/kg GAD in UAN rats. Modest drug accumulation was observed after 28-day chronic treatment.
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