Phosphate as a Determinant of the Difference in Drug Interactions Due to Colestyramine and Colestimide
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- Oda Masako
- Department of Pharmaceutics, School of Pharmaceutical Sciences, Health Sciences University of Hokkaido
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- Kudo Takehiro
- Department of Pharmaceutics, School of Pharmaceutical Sciences, Health Sciences University of Hokkaido
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- Ichimura Yuichi
- Department of Pharmaceutics, School of Pharmaceutical Sciences, Health Sciences University of Hokkaido
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- Saitoh Hiroshi
- Department of Pharmaceutics, School of Pharmaceutical Sciences, Health Sciences University of Hokkaido
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Colestyramine and colestimide have been utilized for lowering serum cholesterol levels in patients with dyslipidemia. They cause drug interactions of different extents, with colestyramine decreasing the absorption of various anionic drugs more potently than colestimide. However, the factors behind the differences in their drug interactions have not yet been fully characterized. We previously reported that colestimide has greater ability than colestyramine to adsorb phosphate. In the present study, we evaluated the binding characteristics of colestyramine and colestimide to several anionic drugs in the absence or presence of phosphate. Resin suspension and drug solution were prepared using ultrapure water, the Japanese Pharmacopeia (JP) 1st fluid or JP 2nd fluid for dissolution testing. After addition of the drug solution to the colestyramine or colestimide suspension, the mixture was gently shaken for 30 min at room temperature and then subjected to high-speed centrifugation. The drug concentration in the resultant supernatant fluid was determined by HPLC. When using ultrapure water as a medium, a much greater level of ibuprofen binding was observed for colestimide than for colestyramine. However, when using the JP 2nd fluid as a medium, almost negligible binding occurred between ibuprofen and colestimide whereas no inhibition of ibuprofen binding to colestyramine was observed. Warfarin, indomethacin, diclofenac, and taurocholic acid showed similar tendencies to ibuprofen. The present results strongly suggest that the much greater interaction of phosphate with colestimide than with colestyramine in the gastrointestinal tract is a possible factor for the weaker drug interactions of colestimide than colestyramine.
収録刊行物
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- 医療薬学
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医療薬学 41 (3), 191-197, 2015
一般社団法人日本医療薬学会
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詳細情報 詳細情報について
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- CRID
- 1390001204777169792
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- NII論文ID
- 130005132602
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- ISSN
- 18821499
- 1346342X
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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
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- 使用不可