Pharmacokinetics of TJ-8117 (Onpi-to), a drug for renal failure (I): Plasma concentration, distribution and excretion of [3H]-(-)epicatechin 3-O-gallate in rats and dogs

Eur J Drug Metab Pharmacokinet. 2004 Apr-Jun;29(2):91-101. doi: 10.1007/BF03190582.

Abstract

TJ-8117 (Onpi-to) is an herbal medicine extracted from a mixture of five crude medicinals (Rhei Rhizoma, Glycyrrhizae Radix, Ginseng Radix, Zingiberis Rhizoma and Aconiti Tuber), which has been developed as a drug for chronic renal failure. (-)Epicatechin 3-O-gallate (ECG), one of the active components of TJ-8117, was labeled with tritium and added to TJ-8117. Pharmacokinetics in plasma, tissue distribution and excretion of radioactivity were investigated following a single oral administration of TJ-8117 containing [3H]ECG ([3H]TJ-8117) in rats and dogs. 1. Following oral administration of [3H]TJ-8117, radioactivity exhibited linear pharmacokinetics in Cmax. Linearity of AUC(0-72 h) was lost at the highest dose of [3H]TJ-8117. Cmax and AUC(0-72 h) were higher in female rats than in male rats, a finding which suggested a sex difference in rats. Plasma levels of radioactivity displayed curves with one peak in dogs, which suggested a species difference between rats and dogs. 2. No accumulation was observed in any tissues in male rats. 3. Within 168 h after administration of [3H]TJ-8117 to male rats, 18.7%, 84.1% and 0.9% of the dose was excreted in urine, feces and expired air, respectively. Data from bile-duct cannulated rats indicated that at least 18.4% of the dose was absorbed.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Area Under Curve
  • Bile / metabolism
  • Blood Proteins / metabolism
  • Catechin / analogs & derivatives*
  • Catechin / blood*
  • Catechin / urine*
  • Dogs
  • Drugs, Chinese Herbal / pharmacokinetics*
  • Feces / chemistry
  • Female
  • Male
  • Protein Binding
  • Rats
  • Rats, Sprague-Dawley
  • Renal Agents / pharmacokinetics*
  • Renal Insufficiency / drug therapy*
  • Tissue Distribution

Substances

  • Blood Proteins
  • Drugs, Chinese Herbal
  • Renal Agents
  • onpi-to
  • Catechin
  • epicatechin gallate