Effect of change of hepatic drug-metabolizing activity on plasma concentrations of major metabolites of the new sleep inducer 450191-S, a 1H-1,2,4-triazolyl benzophenone derivative.
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概要
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Plasma concentrations of the major metabolites of 450191-S, a new sleep inducer which is a 1<I>H</I>-1, 2, 4-triazolyl benzophenone derivative, were determined in rats. Under the HPLC conditions employed, several major metabolites were detected in plasma, and thus the plasma concentration-time profiles for these metabolites were checked in rats in various states. When the animals were pretreated with high doses of 450191-S (200 or 600 mg/kg for 5 or 3 days, respectively) to induce hepatic drug-metabolizing enzymes, plasma concentrations of the metabolites after oral administration of a dose of 200 mg/kg of 450191-S decreased markedly depending on the induced enzyme activity. Pretreatment of rats with phenobarbital also caused decreased plasma levels of metabolites, which were almost the same as those in 450191-S-pretreatment. On the other hand, administration of beta-naphthoflavone to rats led to higher plasma levels of metabolites, and slower elimination compared with those in the control and 450191-S- or phenobarbital-pretreated rats. These results indicate that plasma levels of metabolites are regulated by the drug-metabolizing enzymes in the liver. It also suggests the participation of some specific forms of cytochrome P-450 in the biotransformation of 450191-S and its metabolites.
- 公益社団法人 日本薬理学会の論文
著者
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Touchi Akira
Shionogi & Co. Ltd. Developmental Research Laboratories
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Matsubara Takashi
Shionogi Research Laboratories
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Yamada Noriko
Shionogi Research Laboratories Shionogi & Co. Ltd.
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TOUCHI AKIRA
Shionogi Research Laboratories, Shionogi & Co., Ltd.
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