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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

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Summary

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. 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. 2.

    No accumulation was observed in any tissues in male rats.

  3. 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.

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Authors and Affiliations

  1. Department of Drug Metabolism & Disposition, Research Division, Tsumura & Co., 3586 Yoshiwara, Ami-machi, Inashiki-gun, 300-1192, Ibaraki, Japan

    Yukiho Takizawa, Hiroaki Nishimura, Takashi Morota, Shuichi Takeda & Masaki Aburada

  2. Drug Metabolism and Pharmacokinetics Group, Nemoto Science Co., Ltd., Ibaraki, Japan

    Hiroki Tomisawa

Authors
  1. Yukiho Takizawa
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  2. Hiroaki Nishimura
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  3. Takashi Morota
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  4. Hiroki Tomisawa
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  5. Shuichi Takeda
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  6. Masaki Aburada
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Takizawa, Y., Nishimura, H., Morota, T. et al. 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. European Journal of Drug Metabolism and Pharmacokinetics 29, 91–101 (2004). https://doi.org/10.1007/BF03190582

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  • DOI: https://doi.org/10.1007/BF03190582

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