Unidirectional Inversion of Ibuprofen in Caco-2 Cells : Developing a Suitable Model for Presystemic Chiral Inversion Study(Biopharmacy)
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概要
- 論文の詳細を見る
Intestinal chiral inversion of ibuprofen is still lacking direct evidence. In a preliminary experiment, ibuprofen was found to undergo inversion in Caco-2 cells. This investigation was thus conducted to determine the characteristics and influence of some biochemical factors on the chiral inversion of ibuprofen in Caco-2 cells. The effects of substrate concentration (2.5-40μg/ml), cell density (0.5-2×10^6 cells/well), content of serum (0-20%), coexistence of S ibuprofen (corresponding doses), sodium azide (10mM), exogenous Coenzyme A (CoA)(0.1-0.4mM), and palmitic acid (5-25μM) on inversion were examined. A stereoselective HPLC method based on the Chromasil-CHI-TBB column was developed for quantitative analysis of the drug in cell culture medium. The inversion ratio (F_i) and elimination rate constant were calculated as the indexes of inversion extent. Inversion of ibuprofen in Caco-2 cells was found to be both dose and cell density dependent, indicating saturable characteristics. Addition of serum significantly inhibited the inversion, to an extent of 2.7 fold decrease at 20% content. Preexistence of S enantiomer exerted a significant inhibitory effect (p<0.01 for all tests). Sodium azide decreased the inversion ratio from 0.43 to 0.32 (p<0.01). Exogenous CoA and palmitic acid significantly promoted the inversion at all tested doses (p<0.01 for all tests). This research provided strong evidence to the capacity and capability of intestinal chiral inversion. Although long incubation times up to 120 h were required, Caco-2 cells should be a suitable model for chiral inversion research of 2-APAs considering the human-resourced and well-defined characteristics from the present study.
- 公益社団法人日本薬学会の論文
- 2005-04-01
著者
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WANG Guangji
Key Laboratory of Pharmacokinetics and Drug Metabolism, China Pharmaceutical University
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Wang Guang-ji
Key Laboratory Of Pharmacokinetics And Drug Metabolism China Pharmaceutical University
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Wang Guangji
Key Lab Of Drug Metabolism And Pharmacokinetics China Pharmaceutical University
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Wang Guangji
Key Laboratory Of Drug Metabolism & Pharmacokinetics China Pharmaceutical University
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WU Xiaolan
Key Laboratory of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University
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Roberts Michael
中華人民共和国
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SUN Jianguo
Key Laboratory of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University
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HAO Haiping
Key laboratory of Drug Metabolism and Pharmacokinetics
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Wang Guang-ji
Key Lab Of Drug Metabolism & Pharmacokinetics China Pharmaceutical University
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Wu Xiaolan
Key Lab Of Drug Metabolism & Pharmacokinetics China Pharmaceutical University
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Hao Haiping
Key Lab Of Drug Metabolism And Pharmacokinetics China Pharmaceutical University
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Sun Jianguo
Key Lab Of Drug Metabolism And Pharmacokinetics China Pharmaceutical University
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Sun Jianguo
Key Laboratory Of Drug Metabolism & Pharmacokinetics China Pharmaceutical University
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DING Zuoqi
Key Lab of drug Metabolism & Pharmacokinetics, China Pharmaceutical University
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ROBERTS Michael
Princess Alexandra Hospital, Therapeutics Research Unit, University of Queensland
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Ding Zuoqi
Key Lab Of Drug Metabolism & Pharmacokinetics China Pharmaceutical University
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Hao Haiping
Key Lab Of Drug Metabolism & Pharmacokinetics China Pharmaceutical University
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