Morphine interaction with prasugrel: a double-blind, cross-over trial in healthy volunteers

Background Morphine decreases the concentrations and effects of clopidogrel, which could lead to treatment failure in myocardial infarction. Objectives To clarify whether more potent P2Y 12 -inhibitors may provide an effective alternative, we examined drug–drug interactions between morphine and pras...

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Vydané v:	Clinical research in cardiology Ročník 105; číslo 4; s. 349 - 355
Hlavní autori:	Hobl, Eva-Luise, Reiter, Birgit, Schoergenhofer, Christian, Schwameis, Michael, Derhaschnig, Ulla, Lang, Irene Marthe, Stimpfl, Thomas, Jilma, Bernd
Médium:	Journal Article
Jazyk:	English
Vydavateľské údaje:	Berlin/Heidelberg Springer Berlin Heidelberg 01.04.2016 Springer Nature B.V
Predmet:	Adult Analgesics, Opioid - administration & dosage Analgesics, Opioid - adverse effects Austria Biotransformation Cardiology Chromatography, Liquid Cross-Over Studies Double-Blind Method Drug Interactions Drug Monitoring - methods Female Healthy Volunteers Humans Male Medicine Medicine & Public Health Morphine - administration & dosage Morphine - adverse effects Original Paper Platelet Aggregation - drug effects Platelet Aggregation Inhibitors - administration & dosage Platelet Aggregation Inhibitors - adverse effects Platelet Aggregation Inhibitors - blood Platelet Aggregation Inhibitors - pharmacokinetics Platelet Function Tests Prasugrel Hydrochloride - administration & dosage Prasugrel Hydrochloride - adverse effects Prasugrel Hydrochloride - blood Prasugrel Hydrochloride - pharmacokinetics Purinergic P2Y Receptor Antagonists - administration & dosage Purinergic P2Y Receptor Antagonists - adverse effects Purinergic P2Y Receptor Antagonists - blood Purinergic P2Y Receptor Antagonists - pharmacokinetics Risk Assessment Tandem Mass Spectrometry Young Adult Prasugrel Morphine Platelet function tests Drug interactions Vasodilator-stimulated phosphoprotein
ISSN:	1861-0684, 1861-0692, 1861-0692
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Shrnutí:	Background Morphine decreases the concentrations and effects of clopidogrel, which could lead to treatment failure in myocardial infarction. Objectives To clarify whether more potent P2Y 12 -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.
Bibliografia:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 ObjectType-Undefined-3
ISSN:	1861-0684 1861-0692 1861-0692
DOI:	10.1007/s00392-015-0927-z