Thromb Haemost 2018; 118(12): 2126-2133
DOI: 10.1055/s-0038-1675605
Cellular Haemostasis and Platelets
Georg Thieme Verlag KG Stuttgart · New York

METoclopramide Administration as a Strategy to Overcome MORPHine-ticagrelOr Interaction in PatientS with Unstable Angina PectorIS—The METAMORPHOSIS Trial

Joanna Sikora*
1  Laboratory for Experimental Biotechnology, Collegium Medicum, Nicolaus Copernicus University, Bydgoszcz, Poland
,
Piotr Niezgoda*
2  Department of Cardiology and Internal Medicine, Collegium Medicum, Nicolaus Copernicus University, Bydgoszcz, Poland
,
Malwina Barańska
2  Department of Cardiology and Internal Medicine, Collegium Medicum, Nicolaus Copernicus University, Bydgoszcz, Poland
,
Katarzyna Buszko
3  Department of Theoretical Foundations of Biomedical Science and Medical Informatics, Collegium Medicum, Nicolaus Copernicus University, Bydgoszcz, Poland
,
Natalia Skibińska
2  Department of Cardiology and Internal Medicine, Collegium Medicum, Nicolaus Copernicus University, Bydgoszcz, Poland
,
Wiktor Sroka
4  Department of Medicinal Chemistry, Collegium Medicum, Nicolaus Copernicus University, Bydgoszcz, Poland
,
Krzysztof Pstrągowski
2  Department of Cardiology and Internal Medicine, Collegium Medicum, Nicolaus Copernicus University, Bydgoszcz, Poland
,
Jolanta Siller-Matula
5  Department of Cardiology, Medical University of Vienna, Vienna, Austria
,
Jilma Bernd
6  Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria
,
Diana Gorog
7  National Heart and Lung Institute, Imperial College London, London, United Kingdom
,
Eliano Pio Navarese
1  Laboratory for Experimental Biotechnology, Collegium Medicum, Nicolaus Copernicus University, Bydgoszcz, Poland
8  Inova Center for Thrombosis Research and Drug Development, Inova Heart and Vascular Institute, Fairfax, Virginia, United States
9  SIRIO MEDICINE Research Network, Inova Center for Thrombosis Research and Drug Development, Inova Heart and Vascular Institute, Fairfax, Virginia, United States
,
Michał Piotr Marszałł
4  Department of Medicinal Chemistry, Collegium Medicum, Nicolaus Copernicus University, Bydgoszcz, Poland
,
Jacek Kubica
2  Department of Cardiology and Internal Medicine, Collegium Medicum, Nicolaus Copernicus University, Bydgoszcz, Poland
› Author Affiliations
Further Information

Publication History

17 December 2017

25 September 2018

Publication Date:
19 November 2018 (eFirst)

Abstract

Extensive search for methods of overcoming morphine-related delay of the absorption and onset of action of oral P2Y12 inhibitors in patients presenting with acute coronary syndrome is on-going. The aim of the trial was to investigate whether metoclopramide co-administration could reduce this delay and improve the pharmacokinetics (PKs) and pharmacodynamics (PDs) of ticagrelor and its active metabolite AR-C124900XX. Plasma concentration of both compounds and platelet reactivity were evaluated in nine pre-defined time points within 6 hours after administration of ticagrelor loading dose. The results of our study show that mean platelet activity within the first hour was noticeably higher in metoclopramide-naive patients. Moreover, ticagrelor mean plasma concentration was significantly higher within the initial four time points (15, 30, 45, 60 minutes) in patients receiving metoclopramide (p = 0.039; p = 0.009; p = 0.005; p = 0.008, respectively). To conclude, the co-administration of metoclopramide in patients presenting with unstable angina and treated with morphine, has a beneficial effect on the PK/PD profile of ticagrelor and its metabolite; however, its impact on ST-elevation myocardial infarction patients requires further investigation.