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Published online: 2020-03-18
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Oral NAloxone to overcome the moRphine effect in acute COronary syndrome patients treated with TICagrelor — NARCOTIC trial

Piotr Niezgoda, Malwina A. Barańska, Joanna Sikora, Przemysław Sobczak, Katarzyna Buszko, Adam Sikora, Michał P. Marszałł, Eliano P. Navarese, Bernd Jilma, Jacek Kubica
DOI: 10.5603/CJ.a2020.0040
·
Pubmed: 32207836

open access

Ahead of print
Original articles
Published online: 2020-03-18

Abstract

Background: Numerous worldwide clinical trials have proven the indisputably negative influence of morphine on the pharmacokinetics and pharmacodynamics of P2Y12 receptor inhibitors in patients presenting with acute coronary syndromes. The aim of this trial was to evaluate whether oral co-administration of an anti-opioid agent, naloxone, can be considered a successful approach to overcome ‘the morphine effect’.

Methods: Consecutive unstable angina patients receiving ticagrelor and morphine with or without orally administered naloxone underwent assessment of platelet reactivity using Multiplate analyzer as well as evaluation of the pharmacokinetic profile of ticagrelor and its active metabolite, AR-C124910XX, at nine pre-defined time points within the first 6 hours following oral intake of the ticagrelor loading dose.

Results: The trial shows no significant differences regarding the pharmacokinetics of ticagrelor between both study arms throughout the study period. AR-C124910XX plasma concentration was significantly higher 120 min after the ticagrelor loading dose administration (p = 0.0417). However, the evaluation of pharmacodynamics did not show any statistically significant differences between the study arms.

Conclusions: To conclude, this trial shows that naloxone co-administration in ticagrelor-treated acute coronary syndrome patients on concomitant treatment with morphine shows no definite superiority in terms of ticagrelor pharmacokinetic and pharmacodynamic profile.

Abstract

Background: Numerous worldwide clinical trials have proven the indisputably negative influence of morphine on the pharmacokinetics and pharmacodynamics of P2Y12 receptor inhibitors in patients presenting with acute coronary syndromes. The aim of this trial was to evaluate whether oral co-administration of an anti-opioid agent, naloxone, can be considered a successful approach to overcome ‘the morphine effect’.

Methods: Consecutive unstable angina patients receiving ticagrelor and morphine with or without orally administered naloxone underwent assessment of platelet reactivity using Multiplate analyzer as well as evaluation of the pharmacokinetic profile of ticagrelor and its active metabolite, AR-C124910XX, at nine pre-defined time points within the first 6 hours following oral intake of the ticagrelor loading dose.

Results: The trial shows no significant differences regarding the pharmacokinetics of ticagrelor between both study arms throughout the study period. AR-C124910XX plasma concentration was significantly higher 120 min after the ticagrelor loading dose administration (p = 0.0417). However, the evaluation of pharmacodynamics did not show any statistically significant differences between the study arms.

Conclusions: To conclude, this trial shows that naloxone co-administration in ticagrelor-treated acute coronary syndrome patients on concomitant treatment with morphine shows no definite superiority in terms of ticagrelor pharmacokinetic and pharmacodynamic profile.

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Keywords

acute coronary syndrome, unstable angina, ticagrelor, morphine, naloxone

About this article
Title

Oral NAloxone to overcome the moRphine effect in acute COronary syndrome patients treated with TICagrelor — NARCOTIC trial

Journal

Cardiology Journal

Issue

Ahead of print

Article type

Research paper

Published online

2020-03-18

DOI

10.5603/CJ.a2020.0040

Pubmed

32207836

Keywords

acute coronary syndrome
unstable angina
ticagrelor
morphine
naloxone

Authors

Piotr Niezgoda
Malwina A. Barańska
Joanna Sikora
Przemysław Sobczak
Katarzyna Buszko
Adam Sikora
Michał P. Marszałł
Eliano P. Navarese
Bernd Jilma
Jacek Kubica

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