Drug-drug interaction of cefiderocol, a siderophore cephalosporin, via human drug transporters
| العنوان: | Drug-drug interaction of cefiderocol, a siderophore cephalosporin, via human drug transporters |
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| المؤلفون: | Martha Hernandez-Illas, Yukitoshi Narukawa, Shiro Miyazaki, Takayuki Katsube, Toshihiro Wajima |
| المصدر: | European Journal of Clinical Pharmacology. 74:931-938 |
| بيانات النشر: | Springer Science and Business Media LLC, 2018. |
| سنة النشر: | 2018 |
| مصطلحات موضوعية: | Adult, Male, 0301 basic medicine, Adolescent, Organic anion transporter 1, 030106 microbiology, Siderophores, Pharmacology, 030226 pharmacology & pharmacy, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Pharmacokinetics, Furosemide, medicine, Humans, Drug Interactions, Pharmacology (medical), Rosuvastatin, Rosuvastatin Calcium, Cross-Over Studies, Organic cation transport proteins, biology, Chemistry, Membrane Transport Proteins, Biological Transport, General Medicine, Middle Aged, Drug interaction, Metformin, Cephalosporins, Organic anion-transporting polypeptide, biology.protein, Female, medicine.drug |
| الوصف: | Cefiderocol, a siderophore cephalosporin, will be used concomitantly with other medications for treatment of bacterial infections. In vitro studies demonstrated inhibition potential of cefiderocol on organic anion transporter (OAT) 1, OAT3, organic cation transporter (OCT) 1, OCT2, multidrug and toxin extrusion (MATE) 2-K, and organic anion transporting polypeptide (OATP) 1B3. The aim of this study was to assess in vivo drug-drug interaction (DDI) potential of cefiderocol using probe substrates for these transporters. DDI potentials of cefiderocol as inhibitors were assessed in a clinical study consisting of 3 cohorts. Twelve or 13 healthy adult subjects per cohort orally received a single dose of furosemide 20 mg (for OAT1/3), metformin 1000 mg (for OCT1/2 and MATE2-K), or rosuvastatin 10 mg (for OATP1B3) with or without co-administration with cefiderocol 2 g every 8 h with 3-h infusion (a total of 3, 6, and 9 doses of cefiderocol with furosemide, metformin, and rosuvastatin, respectively). DDI potentials were assessed based on the pharmacokinetics of the substrates. Ratios (90% confidence intervals) of maximum plasma concentration and area under the plasma concentration-time curve were 1.00 (0.71–1.42) and 0.92 (0.73–1.16) for furosemide, 1.09 (0.92–1.28) and 1.03 (0.93–1.15) for metformin, and 1.28 (1.12–1.46) and 1.21 (1.08–1.35) for rosuvastatin, respectively. Exposures to furosemide or metformin did not change when co-administered with cefiderocol. Slight increase in rosuvastatin exposure was observed with co-administered with cefiderocol, which was not considered to be clinically significant. Each treatment was well tolerated. Cefiderocol has no clinically significant DDI potential via drug transporters. |
| تدمد: | 1432-1041 0031-6970 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::61db1d2f0b294674ab8aa30d516bb1e6Test https://doi.org/10.1007/s00228-018-2458-9Test |
| حقوق: | CLOSED |
| رقم الانضمام: | edsair.doi.dedup.....61db1d2f0b294674ab8aa30d516bb1e6 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14321041 00316970 |
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