Pharmacokinetics of (-)-epicatechin-3-O-gallate, an active component of Onpi-to, in rats

(-)-Epicatechin-3-O-gallate (ECG), a component of Rhei Rhizoma, is one of the active components of Onpi-to, a herbal medicine composed of five crude drugs (Rhei Rhizome, Glycyrrhizae Radix, Ginseng Radix, Zingiberis Rhizoma and Aconiti Tuber), which has been used in patients with chronic renal failure. Pharmacokinetics of ECG was investigated in male rats employing an HPLC-electrochemical detection method. 1. Following oral administration of ECG, ECG plasma levels revealed curves characterized by peaks at 0.065, 0.063 and 0.085 h corresponding to dosages of 12.5, 25.0 and 50.0 mg/kg at mean concentrations of 49.62, 212.89 and 464.04 ng/ml, respectively. Plasma levels subsequently declined bi-exponentially. ECG demonstrated nonlinear pharmacokinetics in terms of C(max) and AUC(0-inf). 2. The absolute bioavailability values (F) were 1.02, 1.47 and 3.30% at doses of 12.5, 25.0, and 50.0 mg/kg, respectively. 3. Following intravenous injection of ECG, plasma levels of ECG decreased with the gamma-elimination half-life (t(1/2gamma)) of 4.03 h. 4. Following oral administration of ECG, urinary levels of ECG were lower than the quantitation limit. Moreover, cumulative excretion of the metabolites, delta-(3,4-dihydroxyphenyl)-gamma-valerolactone and delta-(3-methoxy-4-hydroxyphenyl)-gamma-valerolactone, was 2.45 and 0.23% of dose, respectively, up to 30 h after dosing.