Does morphine administration affect ticagrelor conversion to its active metabolite in patients with acute myocardial infarction? A sub-analysis of the randomized, double-blind, placebo- -controlled IMPRESSION trial

Adamski, Piotr; Ostrowska, Małgorzata; Sroka, Wiktor Dariusz; Marszałł, Michał Piotr; Kolasińska, Emilia; Lisiecka, Paulina; Skibińska, Natalia; Sobczak, Przemysław; Szarwas, Paulina; Kubica, Jacek; Koziński, Marek

doi:10.5603/fmc.2015.0003

Cited by 5 publications

(7 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Although the underlying mechanism of these findings was not investigated in detail, it seems most likely that morphine impairs absorption of ticagrelor [39]. Moreover in the subanalysis of the IMPRESSION study, we did not find any evidence that the extent of ticagrelor conversion to AR-C124910XX is affected by morphine administration [41]. Decreased exposure to AR-C124910XX in the morphine arm compared with the placebo arm of the study was most likely caused by a proportional attenuation of exposure to the parent drug.…”

Section: Morphine and Novel Oral P2y12 Inhibitorsmentioning

confidence: 56%

Impact of morphine on antiplatelet effects of oral P2Y12 receptor inhibitors

Kubica

Jilma

et al. 2016

International Journal of Cardiology

Self Cite

View full text Add to dashboard Cite

Morphine and P2Y12 receptor inhibitors are both recommended in patients with acute myocardial infarction. Morphine may impede gastrointestinal absorption of several oral drugs including P2Y12 platelet receptor inhibitors. The aim of this review was to critically discuss drug-drug interactions between oral P2Y12 receptor inhibitors and morphine according to currently available knowledge based on the findings of experimental, observational and randomized clinical studies. The morphine-clopidogrel pharmacodynamic interaction has been observed in numerous trials and it has been proposed as an explanation for the negative impact of morphine on the clinical outcomes in patients with acute coronary syndromes. An analogous morphine interaction with ticagrelor and prasugrel was found in several observational studies and finally proven in randomized trials in healthy volunteers and acute myocardial infarction patients. Morphine delays and attenuates exposure and antiplatelet action of oral P2Y12 receptor inhibitors in patients with myocardial infarction. Although this interaction may have potentially harmful consequences, routine avoidance of morphine cannot be recommended until clinically powered trials are completed.

show abstract

Section: Morphine and Novel Oral P2y12 Inhibitorsmentioning

confidence: 56%

Impact of morphine on antiplatelet effects of oral P2Y12 receptor inhibitors

Kubica

Jilma

et al. 2016

International Journal of Cardiology

Self Cite

View full text Add to dashboard Cite

show abstract

“…Strong CYP3A inducers and inhibitors greatly affect pharmacokinetics of ticagrelor and its active metabolite, thus their co-administration with ticagrelor is contraindicated 19 , 20 . In healthy volunteers the bioavailability of AR-C124910XX ranges from 35% to 40% of ticagrelor plasma concentration, whereas in patients with AMI it may be as low as 21% during the initial hours of treatment 8 , 9 , 21 . Although ticagrelor may increase bioavailability of some statins, currently there are no data indicating that any of the medications routinely used for the treatment of ACS may affect metabolism of ticagrelor 22 .…”

Section: Introductionmentioning

confidence: 99%

“…Although ticagrelor may increase bioavailability of some statins, currently there are no data indicating that any of the medications routinely used for the treatment of ACS may affect metabolism of ticagrelor 22 . This also applies to morphine, the elementary analgesic used to relive chest pain in patients with ACS 21 . Therefore, it remains obscure what causes this discrepancy in the bioavailability of AR-C124910XX between healthy subjects and patients with ACS.…”

Section: Introductionmentioning

confidence: 99%

Metabolism of ticagrelor in patients with acute coronary syndromes

Adamski

Buszko

Sikora

et al. 2018

Sci Rep

Self Cite

View full text Add to dashboard Cite

Ticagrelor is a state-of-the-art antiplatelet agent used for the treatment of patients with acute coronary syndromes (ACS). Unlike remaining oral P2Y12 receptor inhibitors ticagrelor does not require metabolic activation to exert its antiplatelet action. Still, ticagrelor is extensively metabolized by hepatic CYP3A enzymes, and AR-C124910XX is its only active metabolite. A post hoc analysis of patient-level (n = 117) pharmacokinetic data pooled from two prospective studies was performed to identify clinical characteristics affecting the degree of AR-C124910XX formation during the first six hours after 180 mg ticagrelor loading dose in the setting of ACS. Both linear and multiple regression analyses indicated that ACS patients presenting with ST-elevation myocardial infarction or suffering from diabetes mellitus are more likely to have decreased rate of ticagrelor metabolism during the acute phase of ACS. Administration of morphine during ACS was found to negatively influence transformation of ticagrelor into AR-C124910XX when assessed with linear regression analysis, but not with multiple regression analysis. On the other hand, smoking appears to increase the degree of ticagrelor transformation in ACS patients. Mechanisms underlying our findings and their clinical significance warrant further research.

show abstract

“… 16–18 The negative impact of morphine on the intestinal absorption has been proposed as an explanation for the observed interactions, while no evidence was found in support of the influence of morphine on conversion of ticagrelor into its active metabolite. 18 19 Importantly, STEMI, as opposed to NSTEMI, has also been postulated to affect ticagrelor pharmacokinetics. Franchi et al 20 reported that ticagrelor exposure is attenuated and delayed in patients with STEMI receiving morphine and opioid-naive STEMI subjects.…”

Section: Introductionmentioning

confidence: 99%

Comparison of Ticagrelor Pharmacokinetics and Pharmacodynamics in STEMI and NSTEMI Patients (PINPOINT): protocol for a prospective, observational, single-centre study

et al. 2017

Self Cite

View full text Add to dashboard Cite

IntroductionThe most common classification of acute myocardial infarction (AMI) is based on electrocardiographic findings and distinguishes ST-elevation myocardial infarction (STEMI) and non-ST-elevation myocardial infarction (NSTEMI). Both types of AMI differ concerning their epidemiology, clinical approach and early outcomes. Ticagrelor is a P2Y12 receptor inhibitor, constituting the first-line treatment for STEMI and NSTEMI. According to available data, STEMI may be associated with lower plasma concentration of ticagrelor in the first hours of AMI, but currently there are no studies directly comparing ticagrelor pharmacokinetics or antiplatelet effect in patients with STEMI versus NSTEMI.Methods and analysisThe PINPOINT study is a phase IV, single-centre, investigator-initiated, prospective, observational study designed to compare the pharmacokinetics and pharmacodynamics of ticagrelor in patients with STEMI and NSTEMI assigned to the invasive strategy of treatment. Based on an internal pilot study, the trial is expected to include at least 23 patients with each AMI type. All subjects will receive a 180 mg loading dose of ticagrelor. The primary end point of the study is the area under the plasma concentration-time curve (AUC(0–6)) for ticagrelor during the first 6 hours after the loading dose. Secondary end points include various pharmacokinetic features of ticagrelor and its active metabolite (AR-C124910XX), and evaluation of platelet reactivity by the vasodilator-stimulated phosphoprotein assay and multiple electrode aggregometry. Blood samples for the pharmacokinetic and pharmacodynamic assessment will be obtained at pretreatment, 30 min, 1, 2, 3, 4, 6 and 12 hours post-ticagrelor loading dose.Ethics and disseminationThe study received approval from the Local Ethics Committee (Komisja Bioetyczna Uniwersytetu Mikołaja Kopernika w Toruniu przy Collegium Medicum im. Ludwika Rydygiera w Bydgoszczy; approval reference number KB 617/2015). The study results will be disseminated through conference presentations and peer-reviewed journals.Trial registration numberNCT02602444; Pre-results.

show abstract

Does morphine administration affect ticagrelor conversion to its active metabolite in patients with acute myocardial infarction? A sub-analysis of the randomized, double-blind, placebo- -controlled IMPRESSION trial

Cited by 5 publications

References 19 publications

Impact of morphine on antiplatelet effects of oral P2Y12 receptor inhibitors

Impact of morphine on antiplatelet effects of oral P2Y12 receptor inhibitors

Metabolism of ticagrelor in patients with acute coronary syndromes

Comparison of Ticagrelor Pharmacokinetics and Pharmacodynamics in STEMI and NSTEMI Patients (PINPOINT): protocol for a prospective, observational, single-centre study

Contact Info

Product

Resources

About