| アブストラクト | We present 3 patients diagnosed with rhabdomyolysis 1-6 months after the initiation of concomitant rosuvastatin and ticagrelor medication. A literature review and Food and Drug Administration adverse event reporting system revealed >40 reports of rhabdomyolysis during concomitant ticagrelor and rosuvastatin, including 3 with a fatal outcome. We show that ticagrelor inhibits breast cancer resistance protein-, organic anion transporting polypeptide (OATP) 1B1-, 1B3- and 2B1-mediated transport of rosuvastatin in vitro with half-maximal unbound inhibitory concentrations of 0.36, 4.13, 7.5 and 3.26 muM, respectively. A static drug interaction model predicted that ticagrelor may inhibit intestinal breast cancer resistance protein and thus increase rosuvastatin plasma exposure 2.1-fold, whereas the OATP-mediated hepatic uptake of rosuvastatin should not be inhibited due to relatively low portal ticagrelor concentrations. Taken together, concomitant use of ticagrelor with rosuvastatin may increase the systemic exposure to rosuvastatin and the risk of rosuvastatin-induced rhabdomyolysis. Further studies are warranted to investigate the potential pharmacokinetic interaction between ticagrelor and rosuvastatin in humans. |
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| ジャーナル名 | British journal of clinical pharmacology |
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| 投稿日 | 2023/2/7 |
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| 投稿者 | Lehtisalo, Minna; Kiander, Wilma; Filppula, Anne M; Deng, Feng; Kidron, Heidi; Korhonen, Mari; Sinkko, Johanna; Koivula, Kimmo; Niemi, Mikko |
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| 組織名 | Department of Clinical Pharmacology, University of Helsinki, Helsinki, Finland.;Individualized Drug Therapy Research Program, University of Helsinki, Helsinki,;Finland.;Department of Clinical Pharmacology, HUS Diagnostic Center, Helsinki University;Hospital, Helsinki, Finland.;Division of Pharmaceutical Biosciences, Faculty of Pharmacy, University of;Helsinki, Helsinki, Finland.;Pharmaceutical Sciences Laboratory, Faculty of Science and Engineering, Abo;Akademi University, Turku, Finland.;Genetics Laboratory, HUS Diagnostic Center, Helsinki University Hospital,;Helsinki, Finland.;South Karelia Central Hospital, Lappeenranta, Finland. |
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| Pubmed リンク | https://www.ncbi.nlm.nih.gov/pubmed/36740817/ |
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