TOXICOKINETICS OF PHENOBARBITAL IN RATS WITH DL-ETHIONINE-INDUCED LIVER INJURY

概要

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The toxicokinetic parameters of phenobarbital(PB) were assessed in a female rat model of liver disease. In a preliminary study to determine the optimum dose of DL-ethionine(ET) for creating liver damage, intraperitoneal injection of 250, 500, or 1,000 mg/kg of ET was done for 4 days. ET treatment caused an increase in serum GOT and GPT activity and a decrease in the serum glucose concentration. In the liver, triglycerides and free fatty acids were increased and glucose and S-adenosyl-methionine(SAM) were decreased. Histologic examination revealed diffuse fatty degeneration of the hepatocytes. These findings accorded with those already reported as characteristic of ET intoxication. The toxicokinetic parameters for PB were determined after oral or intravenous administration of 100 mg/kg of PB to rats with ET (500 mg/kg, i.p.)-induced hepatotoxicity. After oral administration of PB, prolongation of the Tmax, increased AUC_<0_∞>, and decreased ke and CL values were noted in ET-treated rats. When PB was given intravenously, the AUC_<0_∞> was increased while the values of α, β and CL were decreased. A high level of urinary excretion of PB persisted for 48 hr. Protein binding of PB was unchanged in ET-treated animals, but the extent of bioavailability of PB tended to increase. These results indicate that elimination of PB was impaired in the ET-treated rats.
日本トキシコロジー学会の論文
1993-11-25