Potential of Lansoprazole as a Novel Probe for Cytochrome P450 3A Activity by Measuring Lansoprazole Sulfone in Human Liver Microsomes

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概要

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• Cytochrome P450 (CYP) 3A enzymes are responsible for the metabolism of many drugs. It is useful to know CYP3A activity in individual patients undergoing drug therapy so as to predict the efficacies or adverse events. Lansoprazole is metabolized to Lansoprazole sulfone (LS) by CYP3A, while to 5-hydroxylansoprasole by CYP2C19. The aim of this study was to evaluate whether lansoprazole can be used to assess CYP 3A activity in human liver. Lansoprazole sulfoxidation activity in 14 human liver microsomes was determined as the ratio of lansoprazole/LS, measuring these parameters by high-performance liquid chromatography. Testosterone 6β-hydroxylation (T6β-OH) activity, a known marker for CYP3A activity was also measured together with lansoprazole sulfoxidation activity. Lansoprazole sulfoxidation activity was also analyzed in microsomes preincubat-ed with anti-CYP2C19 antibody. Interindividual variation was observed in lansoprazole sulfoxidation activity and T6β-OH activities of those microsomes, respectively. Lansoprazole sulfoxidation activity was significantly correlated with T6β-OH activity and CYP3A protein level. Lansoprazole sulfoxidation activity in microsomes with anti-CYP2C19 antibody was closely correlated with T6β-OH activity. In contrast, lansoprazole 5-hydroxylation activity was correlated with the CYP2C19 activity. These results suggest that metabolism of lansoprazole to LS by CYP3A occurs independently of metabolism by CYP2C19. LS can be used as a new marker of CYP3A activity.

• 公益社団法人　日本薬学会の論文

著者

• TAKEBA Yuko

  Department of Pharmacology, St. Marianna University School of Medicine

• KUMAI Toshio

  Department of Pharmacology, St. Marianna University School of Medicine

• MATSUMOTO Naoki

  Department of Pharmacology, St. Marianna University School of Medicine

• YANAGIDA Yohei

  Department of Pharmacology, St. Marianna University School of Medicine

• KOBAYASHI Shinichi

  Department of Pharmacology, St. Marianna University School of Medicine

• SUZUKI Satoshi

  Research Institute of Angiocardiology and Cardiovascular Clinic,Faculty of Medicine,Kyushu Universit

• Matsumoto Naoki

  Department Of Cardiology St. Marianna University School Of Medicine

• WATANABE Minoru

  Department of Pharmacology, St. Marianna University School of Medicine

• Hayashi Mikihito

  Department of Pharmacology, St. Marianna University School of Medicine

• Watanabe Mayumi

  Medicinal Safety Research Laboratories Sankyo Co. Ltd.

• Kobayashi Shinichi

  Department Of Pharmacology School Of Medicine Showa University:shionogi Research Laboratories Shiono

• Watanabe M

  The Institute Of Environmental Toxicology

• Takeba Yuko

  Dep. Of Pharmacology St. Marianna Univ. School Of Medicine

• Kumai Toshio

  Department Of Pharmacology St Marianna University School Of Medicine

• Kinoshita Yuichi

  Department of Pharmacology, St. Marianna University School of Medicine, Japan

• Watanabe Minoru

  Department Of Molecular And Cellular Pharmacology Nagoya City University

• Watanabe Minoru

  Dep. Of Pharmacology St. Marianna Univ. School Of Medicine

• Kobayashi Shinichi

  Department Of Biomedical Engineering Graduate School Of Medicine University Of Tokyo

• Yoshida Yutoku

  Dep. Of Pharmacogenomics St. Marianna Univ. Graduate School Of Medicine Jpn

• Yanagida Yohei

  Department Of Pharmacogenomics St. Marianna University Graduate School Of Medicine

• Watanabe Minoru

  Department Of Chemical Pharmacolgy Faculty Of Pharmaceutical Sciences Nagoya City University

• Kinoshita Yuichi

  Department Of Pharmacology St. Marianna University School Of Medicine

• Takeba Yuko

  Department Of Pharmacology St. Marianna University School Of Medicine

• Kumai Toshio

  Department of Pharmacogenomics, St. Marianna University School of Medicine

• Matsumoto Naoki

  Department of Anesthesia, Gunma Prefectural Cardiovascular Center

• Kinoshita Yuichi

  Department of Pathology II, Kansai Medical University, 10-15 Fumizono, Moriguchi, Osaka 570-8506, Japan

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