• Sophie Degrauwe, Marco Roffi, Nathalie Lauriers, Olivier Muller, Pier Giorgio Masci, Marco Valgimigli, and Juan F Iglesias.
• Department of Cardiology, Geneva University Hospital, Rue Gabrielle-Perret-Gentil 4, Geneva, Switzerland.
• Eur Heart J Cardiovasc Pharmacother. 2019 Jul 1; 5 (3): 158-163.

AimsRecent evidence demonstrates that intravenous morphine significantly reduces absorption and delays onset of action of oral P2Y12 receptor inhibitors in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (pPCI). We aimed to assess the influence of intravenous fentanyl compared with morphine on pharmacokinetics and pharmacodynamics of ticagrelor and its active metabolite (AR-C124910XX) in patients undergoing pPCI for STEMI.Methods And ResultsSingle-centre, prospective, open-label, randomized controlled study that will randomly assign in a 1:1 ratio patients with STEMI undergoing pPCI to receive intravenous fentanyl or morphine following a pre-hospital 180-mg loading dose of ticagrelor (ClinicalTrials.gov Identifier: NCT02531165). Pharmacokinetic and pharmacodynamic analyses will be performed at baseline and 1, 2, 4, 6, and 12 h post-loading dose. Pharmacodynamic assessments will include P2Y12 reaction units (PRU) measured by VerifyNow P2Y12. Pharmacokinetic assessments include determination of maximal observed plasma concentrations, time for maximal plasma concentration, and area under the plasma concentration vs. time curve from time 0 to the last measurable concentration (AUC0-t) for ticagrelor and AR-C124910XX. The primary endpoint is platelet reactivity assessed by PRU at 2 h post ticagrelor loading dose.ConclusionPERSEUS will provide randomized data regarding the impact of fentanyl administration, in patients with STEMI undergoing pPCI, on platelet inhibition and ticagrelor absorption and total exposure.Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2018. For permissions, please email: journals.permissions@oup.com.

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