{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T19:09:34Z","timestamp":1769108974074,"version":"3.49.0"},"reference-count":36,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2015,11,23]],"date-time":"2015-11-23T00:00:00Z","timestamp":1448236800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Investigator Sponsored Study Programme of AstraZeneca"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Eur J Clin Investigation"],"published-print":{"date-parts":[[2016,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Our recent drug interaction trial with clopidogrel shows that morphine decreases the concentrations and pharmacodynamic effects of clopidogrel, which could lead to treatment failure in susceptible individuals.<\/jats:p><jats:p>We hypothesized that the pharmacodynamic consequences of drug\u2013drug interactions would be less between morphine and ticagrelor.<\/jats:p><\/jats:sec><jats:sec><jats:title>Materials and methods<\/jats:title><jats:p>Twenty\u2010four healthy subjects received a loading dose of 180 mg ticagrelor together with placebo or 5 mg morphine intravenously in a randomized, double\u2010blind, placebo\u2010controlled, crossover trial. Pharmacokinetics were determined by liquid chromatography tandem mass spectrometry, and ticagrelor pharmacodynamic effects were measured by platelet function tests (whole blood platelet aggregation: multiplate, platelet plug formation: <jats:styled-content style=\"fixed-case\">PFA<\/jats:styled-content>\u2010100, vasodilator\u2010stimulated phosphoprotein (<jats:styled-content style=\"fixed-case\">VASP<\/jats:styled-content>) phosphorylation assay).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Concomitant i.v. injection of morphine slows drug resorption of ticagrelor and its active metabolite (<jats:italic>P<\/jats:italic> &lt; 0\u00b705) by 1 h and decreases plasma levels of ticagrelor and its active metabolite by 25\u201331% (<jats:italic>P<\/jats:italic> \u2264 0\u00b703) and the drug exposure (area under the curve) by 22\u201323% (<jats:italic>P<\/jats:italic> \u2264 0\u00b701). Importantly, however, the pharmacodynamic effects of ticagrelor on platelet aggregation in whole blood, platelet plug formation and <jats:styled-content style=\"fixed-case\">VASP<\/jats:styled-content> phosphorylation are not affected by morphine.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Morphine co\u2010administration moderately decreases ticagrelor plasma concentrations but does not inhibit its pharmacodynamic effects in healthy volunteers within 6 h after drug administration.<\/jats:p><jats:p>Limitations of our trial include the investigation in healthy volunteers under standardized conditions, which does not necessarily reflect a realistic emergency scenario.<\/jats:p><\/jats:sec>","DOI":"10.1111\/eci.12550","type":"journal-article","created":{"date-parts":[[2015,10,9]],"date-time":"2015-10-09T12:29:01Z","timestamp":1444393741000},"page":"7-14","source":"Crossref","is-referenced-by-count":48,"title":["Morphine decreases ticagrelor concentrations 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