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Pharmacokinetic analysis of in vivo metabolism of amino acid or dipeptide conjugates of salicylic acid in rabbit intestinal microorganisms


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タイトル: Pharmacokinetic analysis of in vivo metabolism of amino acid or dipeptide conjugates of salicylic acid in rabbit intestinal microorganisms
著者: Nishida, Koyo / Kido, Mitsuhiko / Sasaki, Hitoshi / Nakamura, Junzo
発行日: 1994年 1月
出版者: Springer Netherlands
引用: Pharmaceutical Research, 11 (1), 160-174, 1994
抄録: We analyzed the pharmacokinetics of salicylic acid (SA)-amino acid (alanine, glutamic acid, methionine, and tyrosine) or SA-dipeptide (glycylglycine) conjugates in rabbits, by using a model that takes into account the metabolism of prodrug to SA by intestinal microorganisms and, also, by model-independent analysis. The blood concentration profiles of these prodrugs and released SA following intracecal and oral administration to rabbits were obtained previously (Nakamura et al., J. Pharm. Pharmacol., 44, 295-299, 1992; Chem. Pharm. Bull., 40, 2164-2168, 1992; Int. J. Pharm., 87, 59-66, 1992; J. Pharm. Pharmacol., 44, 713-716, 1992). First, the overall in vivo behavior was evaluated by statistical moment analysis. Next, the blood concentration profiles of prodrug and SA following intracecal and oral administration were simultaneously fitted to the above model. In general, good agreement was observed between fitted lines and experimental data for every prodrug, suggesting the validity of this model. The obtained parameters characterized the difference in the rate of metabolism and absorption among the prodrugs. Lower absorbability and enhanced hydrolysis rate of the prodrug lead to prolonged blood concentration of SA.
記述: without figures / グラフなし
キーワード: pharmacokinetic analysis / salicylic acid / prodrug / metabolism / rabbit / intestinal microorganism
URI: http://hdl.handle.net/10069/6485
ISSN: 07248741
DOI: 10.1023/A:1018926618070
PubMed ID: 8140048
関連リンク : http://dx.doi.org/10.1023/A:1018926618070
権利: The original publication is available at www.springerlink.com
資料タイプ: Journal Article
原稿種類: author
出現コレクション:050 学術雑誌論文

引用URI : http://hdl.handle.net/10069/6485

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