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.
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.
Takizawa
Yukiho
Y
Department of Drug Metabolism & Disposition, Research Division, Tsumura & Co., Inashiki-gun, Ibaraki, Japan.
Nishimura
Hiroaki
H
Morota
Takashi
T
Tomisawa
Hiroki
H
Takeda
Shuichi
S
Aburada
Masaki
M
D000818:Animals; D019540:Area Under Curve; D001646:Bile / Q000378:metabolism; D001798:Blood Proteins / Q000378:metabolism; D002392:Catechin / Q000031:analogs & derivatives* / Q000097:blood* / Q000652:urine*; D004285:Dogs; D004365:Drugs, Chinese Herbal / Q000493:pharmacokinetics*; D005243:Feces / Q000737:chemistry; D005260:Female; D008297:Male; D011485:Protein Binding; D051381:Rats; D017207:Rats, Sprague-Dawley; D012076:Renal Agents / Q000493:pharmacokinetics*; D051437:Renal Insufficiency / Q000188:drug therapy*; D014018:Tissue Distribution
D001798:Blood Proteins; D004365:Drugs, Chinese Herbal; D012076:Renal Agents; C093447:onpi-to; D002392:Catechin; C062669:epicatechin gallate