Pharmacokinetics of conjugated metabolites in rat plasma after oral administration of tectoridin

Abstract

Tectoridin is a major isoflavone found in the flowers of Pueraria thomsonii Benth. It possesses estrogenic, hypoglycemic, anti-oxidant, and anti-inflammatory activities. In the present study, we evaluated the plasma pharmacokinetic profile of tectoridin in rats. We isolated a new metabolite, tectorigenin-7-O-glucuronide-4′-O-sulfate (Te-7G-4′S), from the bile of rats treated orally with tectoridin and determined its chemical structure by spectral analysis. Furthermore, we developed a selective and accurate method for the simultaneous quantification of tectoridin metabolites, including Te-7G-4′S, tectorigenin-7-O-glucuronide (Te-7G), tectorigenin-7-O-sulfate (Te-7S), and tectorigenin in rat plasma, and measured their plasma concentrations in rats orally administered tectoridin (200mg/kg). Plasma concentrations of Te-7G-4′S, Te-7G, Te-7S, and tectorigenin reached maximal values of 21.4±13.8μmol at 3.50±1.87h, 20.5±9.7μmol at 3.17±1.81h, 14.3±3.3μmol at 5.58±3.07h, and 8.67±3.07μmol at 4.92±2.87h, respectively. Enterohepatic recirculation resulted in double peaks or a flat concentration curve/time profile of the metabolites. Since plasma concentrations of tectorigenin conjugated metabolites were higher than those of the tectorigenin aglycone, it can be concluded that extensive phase II metabolism plays an important role in the pharmacokinetics of tectoridin and tectorigenin in vivo.