Dose-Dependent Pharmacokinetics and First-Pass Metabolism of Acetaminophen in Rats
スポンサーリンク
概要
- 論文の詳細を見る
In order to investigate the in vivo first-pass metabolism of acetaminophen (AAP) following the oral and intraduodenal administration in rats, a pharmacokinetic compartment model including absorption process was developed. Using the parameters for the disposition kinetics of AAP and its metabolites, sulfate and glucuronide, which were determined in the separate study, the extent of the first-pass metabolism and the contribution of sulfation and glucuronidation to the total first-pass metabolism in vivo were quantitatively estimated. As for the results, the first-pass metabolism of AAP following the oral and intraduodenal administration ws mainly attributable to the sulfoconjugation pathway in rats. The sulfation of AAP in the intestine and/or in the liver during the first-pass was proved to be a saturable process. Then, the sulfation in the first-pass metabolism showed the dose-and absorption rate-dependent kinetics. Thus, the pharmacokinetic model including the absorption process proposed in the present study was proved to be valid and useful for the estimation of in vivo first-pass metabolism of AAP in rats.
- 公益社団法人日本薬学会の論文
著者
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Higashi Y
Institute Of Pharmaceutical Sciences Hiroshima University School Of Medicine
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Higashi Yutaka
Institute Of Pharmaceutical Sciences Hiroshima University School Of Medicine
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Murakami T
Institute Of Pharmaceutical Sciences Hiroshima University School Of Medicine
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Murakami Teruo
Research And Development Center Toshiba Corporation
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Higashi Yutaka
Department Of Pharmaceutics Institute Of Pharmaceutical Sciences Hiroshima University School Of Medi
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Yata Noburu
Faculty Of Pharmaceutical Sciences Fukuyama University:department Of Pharmaceutics Institute Of Phar
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Kawamata Ken'ichiro
Institute Of Pharmaceutical Sciences Hiroshima University School Of Medicine
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Murakami Teruo
Institute Of Pharmaceutical Sciences Hiroshima University School Of Medicine
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Murakami T
Hiroshima Univ. School Of Medicine Hiroshima Jpn
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YATA Noboru
Institute of Pharmaceutical Sciences, Hiroshima University School of Medicine
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Yata Noboru
Institute Of Pharmaceutical Sciences Hiroshima University School Of Medicine:faculty Of Pharmaceutic
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Yata Noboru
Institute Of Pharmaceutical Sciences Hiroshima University
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TONE Yoshito
Institute of Pharmaceutical Sciences, Hiroshima University School of Medicine
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Tone Yoshito
Institute Of Pharmaceutical Sciences Hiroshima University School Of Medicine
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