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Morphine interaction with prasugrel: a double-blind, cross-over trial in healthy volunteers.
Hobl, Eva-Luise; Reiter, Birgit; Schoergenhofer, Christian; Schwameis, Michael; Derhaschnig, Ulla; Lang, Irene Marthe; Stimpfl, Thomas; Jilma, Bernd.
Afiliación
  • Hobl EL; Department of Clinical Pharmacology, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria. eva-luise.hobl@meduniwien.ac.at.
  • Reiter B; Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Vienna, Vienna, Austria.
  • Schoergenhofer C; Department of Clinical Pharmacology, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria.
  • Schwameis M; Department of Clinical Pharmacology, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria.
  • Derhaschnig U; Department of Clinical Pharmacology, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria.
  • Lang IM; Department of Internal Medicine II, Division of Cardiology, Medical University of Vienna, Vienna, Austria.
  • Stimpfl T; Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Vienna, Vienna, Austria.
  • Jilma B; Department of Clinical Pharmacology, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria. bernd.jilma@meduniwien.ac.at.
Clin Res Cardiol ; 105(4): 349-55, 2016 Apr.
Article en En | MEDLINE | ID: mdl-26493304
BACKGROUND: Morphine decreases the concentrations and effects of clopidogrel, which could lead to treatment failure in myocardial infarction. OBJECTIVES: To clarify whether more potent P2Y12-inhibitors may provide an effective alternative, we examined drug-drug interactions between morphine and prasugrel. METHODS: Twelve healthy volunteers received 60 mg prasugrel with placebo or 5 mg morphine intravenously in a randomized, double-blind, placebo-controlled, cross-over trial. Pharmacokinetics were determined by liquid chromatography tandem mass spectrometry, and prasugrel effects were measured by platelet function tests. RESULTS: Morphine neither diminished total drug exposure (AUC), which was the primary endpoint, nor significantly delayed drug absorption of prasugrel. However, morphine reduced maximal plasma concentrations (C max) of prasugrel active metabolite by 31 % (p = 0.019). Morphine slightly, but not significantly, delayed the onset of maximal inhibition of platelet plug formation under high shear rates (30 vs. 20 min). Whole blood aggregation was not influenced. CONCLUSIONS: Although morphine significantly decreases the maximal plasma concentrations of prasugrel active metabolite, it does not diminish its effects on platelets to a clinically relevant degree in healthy volunteers. However, it should be considered that the observed decrease in C max of prasugrel active metabolite caused by morphine co-administration may gain relevance in STEMI patients. CLINICAL TRIAL REGISTRATION: NCT01369186, EUDRA-CT#: 2010-023761-22.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Inhibidores de Agregación Plaquetaria / Agregación Plaquetaria / Antagonistas del Receptor Purinérgico P2Y / Clorhidrato de Prasugrel / Analgésicos Opioides / Morfina Tipo de estudio: Clinical_trials / Etiology_studies / Risk_factors_studies Límite: Adult / Female / Humans / Male País/Región como asunto: Europa Idioma: En Revista: Clin Res Cardiol Asunto de la revista: CARDIOLOGIA Año: 2016 Tipo del documento: Article País de afiliación: Austria Pais de publicación: Alemania

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Inhibidores de Agregación Plaquetaria / Agregación Plaquetaria / Antagonistas del Receptor Purinérgico P2Y / Clorhidrato de Prasugrel / Analgésicos Opioides / Morfina Tipo de estudio: Clinical_trials / Etiology_studies / Risk_factors_studies Límite: Adult / Female / Humans / Male País/Región como asunto: Europa Idioma: En Revista: Clin Res Cardiol Asunto de la revista: CARDIOLOGIA Año: 2016 Tipo del documento: Article País de afiliación: Austria Pais de publicación: Alemania