Pharmacokinetic Differences between Lansoprazole Enantiomers and Contribution of Cytochrome P450 Isoforms to Enantioselective Metabolism of Lansoprazole in Dogs.
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- MASA Kengo
- Department of Pharmacy, Kumamoto University Hospital
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- HAMADA Akinobu
- Department of Pharmacy, Kumamoto University Hospital
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- ARIMORI Kazuhiko
- Department of Pharmacy, Kumamoto University Hospital
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- FUJII Junko
- Department of Pharmacy, Kumamoto University Hospital
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- NAKANO Masahiro
- Department of Pharmacy, Kumamoto University Hospital
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The purpose of this study was to evaluate the pharmacokinetics of lansoprazole enantiomers and contribution of cytochrome P450 enzymes to enantioselective metabolism in dogs. The mean Cmax and area under the curve (AUC) values of (+)-lansoprazole were 4—5 times greater than those of (−)-lansoprazole following oral administration of 30-mg racemic lansoprazole to dogs. The CLtot/F values of (+)-lansoprazole were significantly smaller than those of (−)-lansoprazole (p<0.05). The mean unbound fraction of (−)-lansoprazole was significantly greater than that of the (+)-lansoprazole. The amount of (+)-lansoprazole remaining was significantly greater than that of the (−)-lansoprazole after incubation of racemic lansoprazole in dog liver microsomes. When the effects of ticlopidine or ketoconazole on the metabolism of lansoprazole were studied using dog liver microsomes, ticlopidine significantly inhibited the formation of 5-hydroxylansoprazole, but not another metabolite, lansoprazole sulfone; however ketoconazole significantly inhibited formation of both metabolites. When the amount of (+)- and (−)-enantiomers remaining was measured in the presence and absence of ticlopidine, the amount of (+)-lansoprazole was significantly greater than that of the (−)-lansoprazole. On the other hand, there was no significant difference between the amount of (+)- and (−)-enantiomers remaining in combination with ketoconazole. These results suggest that the enantioselective pharmacokinetics of lansoprazole enantiomers are probably ascribable to their enantioselective protein binding and/or metabolism, and among the cytochrome P450 enzymes, CYP3A contributed to the enantioselective metabolism of lansoprazole.
収録刊行物
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- Biological & Pharmaceutical Bulletin
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Biological & Pharmaceutical Bulletin 24 (3), 274-277, 2001
公益社団法人 日本薬学会
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詳細情報 詳細情報について
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- CRID
- 1390282679603145600
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- NII論文ID
- 110003663380
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- NII書誌ID
- AA10885497
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- COI
- 1:CAS:528:DC%2BD3MXhs1Omsr8%3D
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- ISSN
- 13475215
- 09186158
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- NDL書誌ID
- 5682587
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- PubMed
- 11256484
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- 本文言語コード
- en
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- データソース種別
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- JaLC
- NDL
- Crossref
- PubMed
- CiNii Articles
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- 抄録ライセンスフラグ
- 使用不可