Abstract 12868: Morphine Decreases Ticagrelor Concentrations but Not Its Effects: A Randomized, Double-Blind, Placebo-Controlled Trial

Abstract

Introduction: Our recent drug interaction trial with clopidogrel showed that morphine decreases the concentrations and effects of clopidogrel, which could lead to treatment failure in susceptible individuals. This study examined possible drug-drug interactions between ticagrelor and morphine. Hypothesis: We hypothesized that the pharmacodynamic consequences of drug-drug interactions would be less between morphine and ticagrelor. Methods: Twenty-four healthy subjects received a loading dose of 180mg ticagrelor together with placebo or 5mg morphine intravenously in a randomized, double-blind, placebo-controlled, cross-over trial. Pharmacokinetics were determined by liquid chromatography tandem mass spectrometry, and ticagrelor effects were measured by platelet function tests. Results: Concomitant i.v. injection of morphine slows drug resorption of ticagrelor and its active metabolite (p<0.05) by one hour and decreases plasma levels of ticagrelor and its active metabolite (by 25-31%; p < 0.03) and the drug exposure (area under the curve by 22-23%; p < 0.01). Importantly, however, the effects of ticagrelor on platelet aggregation in whole blood, platelet plug formation, and vasodilator-stimulated phosphoprotein (VASP) phosphorylation are not affected by morphine. Conclusions: Morphine co-administration moderately decreases ticagrelor plasma concentrations but does not inhibit ist effects. Therefore, a 180 mg loading dose of ticagrelor appears to provide consistent and reliable platelet inhibition when morphine has to be given for pain relief.