Pharmacokinetics of rhein from Onpi-to, an Oriental herbal medicine, in rats.

Onpi-to, an herbal medicine composed of five crude drugs (Rhei Rhizoma, Glycyrrhizae Radix, Ginseng Radix, Zingiberis Rhizoma and Aconiti Tuber), was administered orally to rats. Onpi-to includes 1.240% of total potential rhein derived from sennoside A, sennoside B, rhein 8-O-glucopyranoside and rhein. Plasma, urinary and biliary levels of rhein were determined by an HPLC-UV method. The plasma levels displayed curves characterized by maximum peaks at 8.3+/-5.2 min, 8.3+/-5.2 min and 20.0+/-21.9 min following dosages of 125, 250 and 500 mg/kg with mean concentrations of 1302.5+/-926.4, 2973.6+/-684.3 and 3118.8+/-1701.2 ng/ml, respectively, followed by a subsequent decline. Area under the concentration-time curve (AUC)(0-48 h) at doses of 125, 250 and 500 mg/kg were 752.3+/-321.5, 2443.3+/-554.4 and 4443.2+/-2641.3 ng.h/ml, respectively. In female rats, rhein plasma levels showed curves which had a maximum peak at 45.0+/-16.4 min after a dosage of 250 mg/kg with mean concentration of 3058.0+/-1533.7 ng/ml, followed by a subsequent decline. AUC(0-48 h) was 5537.7+/-1876.0 ng.h/ml. The cumulative urinary excretion of rhein and of conjugated rhein was 3.14+/-1.56% and 38.21+/-18.87% of dose, respectively, 48 h after dosing at 500 mg/kg of Onpi-to in male rats. The cumulative biliary excretion of rhein was 1.34+/-0.44% of dose 48 h after dosing at 500 mg/kg of Onpi-to in male rats.