Eur J Clin Pharmacol (2017) 73:1121–1128 DOI 10.1007/s00228-017-2282-7 PHARMACOKINETICS AND DISPOSITION A pharmacokinetic drug–drug interaction study between selexipag and midazolam, a CYP3A4 substrate, in healthy male subjects 1 1 2 1 Pierre-Eric Juif & Margaux Boehler & Yves Donazzolo & Shirin Bruderer & Jasper Dingemanse Received: 28 April 2017 /Accepted: 7 June 2017 /Published online: 21 June 2017 Springer-Verlag GmbH Germany 2017 Abstract treatment B compared to A for both midazolam (16%) and Purpose In vitro data showed that selexipag and its active 1-hydroxymidazolam (20%). Exposure (area under the curve) metabolite (ACT-333679) have an inductive effect on to midazolam and 1-hydroxymidazolam was similar between CYP3A4, CYP2B6, and CYP2C9 at concentrations approxi- treatments, and the 90% confidence intervals of geometric mately 100-fold higher than the maximum plasma concentra- mean ratios were within the bioequivalence interval. tion (C ) measured under steady-state conditions. In order Treatment with midazolam, selexipag, and the combination max to confirm in vivo the lack of induction at the enterocyte level, was safe and well tolerated. we assessed the effect of selexipag on midazolam, a substrate Conclusion Exposure to midazolam and 1-hydroxymidazolam of hepatic and intestinal CYP3A4. was not affected by treatment with selexipag. Methods This study
European Journal of Clinical Pharmacology – Springer Journals
Published: Jun 21, 2017
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