Sophora flavescens is a Chinese medicinal herb used for the treatment of gastrointestinal hemorrhage, skin diseases, pyretic\r\nstranguria and viral hepatitis. In this study the herb-drug interactions between S. flavescens and indinavir, a protease\r\ninhibitor for HIV treatment, were evaluated in rats. Concomitant oral administration of Sophora extract (0.158 g/kg or\r\n0.63 g/kg, p.o.) and indinavir (40 mg/kg, p.o.) in rats twice a day for 7 days resulted in a dose-dependent decrease of plasma\r\nindinavir concentrations, with 55%ââ?¬â??83% decrease in AUC0-ââ?¬Ë? and 38%ââ?¬â??78% reduction in Cmax. The CL (Clearance)/F (fraction\r\nof dose available in the systemic circulation) increased up to 7.4-fold in Sophora-treated rats. Oxymatrine treatment (45 mg/\r\nkg, p.o.) also decreased indinavir concentrations, while the ethyl acetate fraction of Sophora extract had no effect. Urinary\r\nindinavir (24-h) was reduced, while the fraction of indinavir in faeces was increased after Sophora treatment. Compared to\r\nthe controls, multiple dosing of Sophora extract elevated both mRNA and protein levels of P-gp in the small intestine and\r\nliver. In addition, Sophora treatment increased intestinal and hepatic mRNA expression of CYP3A1, but had less effect on\r\nCYP3A2 expression. Although protein levels of CYP3A1 and CYP3A2 were not altered by Sophora treatment, hepatic CYP3A\r\nactivity increased in the Sophora-treated rats. All available data demonstrated that Sophora flavescens reduced plasma\r\nindinavir concentration after multiple concomitant doses, possibly through hepatic CYP3A activity and induction of\r\nintestinal and hepatic P-gp. The animal study would be useful for predicting potential interactions between natural\r\nproducts and oral pharmaceutics and understanding the mechanisms prior to human studies. Results in the current study\r\nsuggest that patients using indinavir might be cautioned in the use of S. flavescens extract or Sophora-derived products.
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