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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Published in:Clinical research in cardiology Vol. 105; no. 4; pp. 349 - 355
Main Authors: Hobl, Eva-Luise, Reiter, Birgit, Schoergenhofer, Christian, Schwameis, Michael, Derhaschnig, Ulla, Lang, Irene Marthe, Stimpfl, Thomas, Jilma, Bernd
Format: Journal Article
Language:English
Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.04.2016
Springer Nature B.V
Subjects:
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
Online Access:Get full text
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Summary: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.
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ISSN:1861-0684
1861-0692
1861-0692
DOI:10.1007/s00392-015-0927-z