The Effect of Increased Free Concentrations of Warfarin Due to Protein-binding Substitution in a Combination of Tolvaptan on the PT-INR
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- Saito Masayuki
- Department of Pharmacy, Tosei General Hospital Department of Clinical Pharmacy, Graduate School of Pharmaceutical Sciences, Nagoya City University
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- Maeda Tohru
- College of Pharmacy, Kinjo Gakuin University
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- Ichihara Toshihiko
- Department of Emergency Medicine, Tosei General Hospital
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- Iwao Takahiro
- Department of Clinical Pharmacy, Graduate School of Pharmaceutical Sciences, Nagoya City University
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- Suzuki Tadashi
- Department of Clinical Pharmacy, Graduate School of Pharmaceutical Sciences, Nagoya City University
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Abstract
<p>We previously reported that tolvaptan may influence warfarin pharmacodynamics in vivo; however, the mechanism responsible for this influence was not clear. In this study, we investigated the drug-drug interactions between warfarin and tolvaptan by measuring warfarin blood concentrations in 18 patients who received warfarin therapy and in 24 who received warfarin+tolvaptan therapy. The free warfarin concentrations significantly increased in patients who were also receiving oral tolvaptan (p=0.04). In vitro albumin-binding experiments showed that the free warfarin concentrations significantly increased with the addition of tolvaptan, in a dose-dependent manner, through albumin-binding substitution (approximately 2.5 times). Both clinical and in vitro data showed that tolvaptan increased the unbound warfarin serum concentration. The prothrombin time-international normalized ratio (PT-INR) tended to increase within 2 weeks when tolvaptan was added at clinically used doses (p=0.14). Special attention is warranted in cases with a serum tolvaptan concentration of ≥125 ng/mL (≥7.5 mg/d) for at least 2 weeks following oral tolvaptan administration.</p>
Journal
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- YAKUGAKU ZASSHI
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YAKUGAKU ZASSHI 140 (10), 1269-1274, 2020-10-01
The Pharmaceutical Society of Japan
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Details 詳細情報について
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- CRID
- 1390567172583346304
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- NII Article ID
- 130007920203
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- NII Book ID
- AN00284903
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- ISSN
- 13475231
- 00316903
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- NDL BIB ID
- 030682759
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- PubMed
- 32684555
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- Text Lang
- ja
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- Data Source
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- JaLC
- NDL
- Crossref
- PubMed
- CiNii Articles
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- Abstract License Flag
- Disallowed