| アブストラクト | Myopathy is a group of muscle diseases that can be induced or exacerbated by drug-drug interactions (DDIs). We sought to identify clinically important myopathic DDIs and elucidate their underlying mechanisms. Five DDIs were found to increase the risk of myopathy based on analysis of observational data from the Indiana Network of Patient Care. Loratadine interacted with simvastatin (relative risk 95% confidence interval [CI] = [1.39, 2.06]), alprazolam (1.50, 2.31), ropinirole (2.06, 5.00), and omeprazole (1.15, 1.38). Promethazine interacted with tegaserod (1.94, 4.64). In vitro investigation showed that these DDIs were unlikely to result from inhibition of drug metabolism by CYP450 enzymes or from inhibition of hepatic uptake via the membrane transporter OATP1B1/1B3. However, we did observe in vitro synergistic myotoxicity of simvastatin and desloratadine, suggesting a role in loratadine-simvastatin interaction. This interaction was epidemiologically confirmed (odds ratio 95% CI = [2.02, 3.65]) using the data from the US Food and Drug Administration Adverse Event Reporting System. |
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| ジャーナル名 | Clinical pharmacology and therapeutics |
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| Pubmed追加日 | 2015/5/16 |
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| 投稿者 | Han, X; Quinney, S K; Wang, Z; Zhang, P; Duke, J; Desta, Z; Elmendorf, J S; Flockhart, D A; Li, L |
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| 組織名 | Department of Pharmacology and Toxicology, Indiana University at Indianapolis,;Indianapolis, Indiana, USA.;Center for Computational Biology and Bioinformatics, Indiana University at;Indianapolis, Indianapolis, Indiana, USA.;Division of Clinical Pharmacology in the Department of Medicine, Indiana;University at Indianapolis, Indianapolis, Indiana, USA.;Department of Obstetrics and Gynecology, Indiana University at Indianapolis,;Indiana Institute of Personalized Medicine, School of Medicine, Indiana;Department of Medical and Molecular Genetics, Indiana University at Indianapolis,;Regenstrief Institute, Indiana University at Indianapolis, Indianapolis, Indiana,;USA.;Department of Cellular & Integrative Physiology, Indiana University at |
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| Pubmed リンク | https://www.ncbi.nlm.nih.gov/pubmed/25975815/ |
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