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Baicalin (BG) and its aglycone, baicalein (B), are strong antioxidants and have various pharmacological actions and show unique metabolic fates in the rat. The aim of the present study was to evaluate the contribution of multidrug resistance-associated protein 2 (Mrp2, Abcc2) to the disposition of BG after oral administration of B using the Eisai hyperbilirubinemic rat (EHBR, Mrp2-deficient), in comparison with the Sprague-Dawley rat (SD, the wild-type form of EHBR). When B at a dose of 12.1 mg/kg was administered orally to EHBRs, the area under the concentration curve from time 0 to 24 h (AUC(0-24 h)) and C(max) values of plasma BG, 27.6 + or - 3.5 microM x h and 11.4 + or - 3.9 microM, respectively, were significantly higher at 5-fold and 8-fold, respectively, than those (AUC(0-24 h) value of 5.39 + or - 1.37 microM x h and C(max) value of 1.51 + or - 0.38 microM) in SD rats. In addition, when B at a dose of 1.2 mg/kg was injected into the portal vein of EHBRs, a marked reduction in the biliary excretion of BG (6.59 + or - 5.64 nmol) and a marked increase of BG in the systemic circulation (AUC(0-120 min) of 75.4 + or - 34.5 microM x min) were observed, in comparison with those (biliary excretion of 29.7 + or - 9.3 nmol and AUC(0-120 min) value of 2.42 + or - 1.44 microM x min) in SD rats. Thus, it was clarified that after oral administration of B, the markedly higher concentration of plasma BG in EHBRs than in SD rats was caused mainly by a drastic reduction in the biliary excretion of BG and marked enhancement of its sinusoidal efflux from the liver.

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Hepatic Contribution to a Marked Increase in the Plasma Concentration of Baicalin after Oral Administration of Its Aglycone, Baicalein, in Multidrug Resistance-Associated Protein 2-Deficient Rat