Pharmacokinetics of (-)Epicatechin 3-O-Gallate, Glycyrrhetic Acid and Rhein in Healthy Male Volunteers after Multiple Dose Administration of TJ-8117 (Unipito), a Japanese Traditional Medicine for Renal Failure

Aims: Unpito, an herbal medicine extracted from a mixture of five crude medicines (Rhei Rhizoma, Glycyrrhizae Radix, Ginseng Radix, Zingiberis Rhizoma and Aconiti Tuber), has been developed as a drug for chronic renal failure. In general, it is difficult to estimate the absorption and excretion of herbal medicines due to the presence of a wide variety of components. The purpose of the current study was to examine the systemic pharmacokinetics and elimination of Unpito in healthy volunteers following repeated administration as part of the clinical study of the medicine. Methods: Three compounds, (-) epicatechin 3-O-gallate (ECG), glycyrrhetic acid (GA) and rhein (RH) were selected as markers, to examine the clinical pharmacokinetics of Unpito based on their levels in this medicine. The disposition of each compound was evaluated in 24 healthy volunteers receiving multiple oral doses (4, 6, and 8 capsules three times a day). Results: After repeated administration, plasma ECG and GA concentrations were lower than those simulated. RH plasma concentrations were consistent with the simulation, indicating linear pharmacokinetics of RH. The potential accumulations of marker compounds were not observed from the roughly constant plasma concentrations of troughs at 72, 120, and 144 h after the first administration nor from the urinary excretions. Conclusions: This is the first study presenting pharmacokinetics of ECG, GA and RH derived from Unpito, an herbal medicine, in healthy volunteers after multiple dose administration