Pharmacokinetics of TJ-8117(Onpi-to), a drug for renal failure (II): effects of food, repeated administration and renal failure to plasma concentration of [3H]-(-)epicatechin 3-O-gallate in rats.
TJ-8117 (Onpi-to) is a herbal medicine extracted from mixture of five crude drugs (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 compounds of TJ-8117, was labeled with tritium and spiked to TJ-8117. Effects of food, renal failure and repeated administration to pharmacokinetics of ECG-related radioactivity in the plasma were investigated after oral administration of TJ-8117 containing [3H]ECG ([3H]TJ-8117) in male rats. After oral administration of [3H]TJ-8117, the radioactivity in the plasma in non-fasted rats was higher than that in fasted rats. AUC(0-72 h) and Cmax in the non-fasted was 123% and 248% of those in the fasted. After oral administration of [3H]TJ-8117, the radioactivity in the plasma in 5/6 nephrectomized rats was higher than that in sham-operated rats. AUC(0-72 h) and Cmax in 5/6 nephrectomized was 332% and 236% of those in sham-operated. After repeated administration of TJ-8117 for 6 days, [3H]TJ-8117 was administered on 7th day. Radioactivity in plasma in first day was similar to that in 7th day. The pharmacokinetic parameters were not significantly different between single and repeated administration.
Takizawa
Yukiho
Y
Department of Drug Metabolism & Disposition, Research Division, Tsumura & Co, Ami-machi, Inashiki-gun, Ibaraki, Japan.
Morita
Toshimi
T
Fujitsuka
Naoki
N
Kido
Akiko
A
Shindou
Shouichirou
S
Tomisawa
Hiroki
H
Kase
Yoshio
Y
Takeda
Shuichi
S
Aburada
Masaki
M
Miyamoto
Keńtchi
K
D000818:Animals; D002392:Catechin / Q000031:analogs & derivatives* / Q000097:blood; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage / Q000493:pharmacokinetics*; D005502:Food; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D051437:Renal Insufficiency / Q000188:drug therapy / Q000378:metabolism*; D014316:Tritium
D004365:Drugs, Chinese Herbal; C093447:onpi-to; D014316:Tritium; D002392:Catechin; C062669:epicatechin gallate