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

Abstract

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 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 32 healthy volunteers receiving single oral doses (2, 4, 8, and 12 capsules).Results: After a single oral administration, ECG and RH exhibited linear pharmacokinetics in AUC and Cmax, while GA did not exhibit linear pharmacokinetics. A cross-over study was conducted to evaluate the effect of food at a single dose of 4 capsules. The effect of food was observed for the plasma concentrations of ECG and RH, while not for GA. The potential accumulations of δ-(3, 4-dihydroxyphenyl) γ-valerolactone (VL-2), a metabolite of ECG and RH were not observed. GA was not detected in urine.Conclusions: This is the first study presenting pharmacokinetics of ECG, GA and RH derived from Unpito, an herbal medicine, in healthy volunteers after single dose administration.