Oral NAloxone to overcome the moRphine effect in acute COronary syndrome patients treated with TICagrelor - NARCOTIC trial.
acute coronary syndrome
morphine
naloxone
ticagrelor
unstable angina
Journal
Cardiology journal
ISSN: 1898-018X
Titre abrégé: Cardiol J
Pays: Poland
ID NLM: 101392712
Informations de publication
Date de publication:
2022
2022
Historique:
received:
24
09
2019
accepted:
25
02
2020
pubmed:
25
3
2020
medline:
7
6
2022
entrez:
25
3
2020
Statut:
ppublish
Résumé
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 coadministration of an anti-opioid agent, naloxone, can be considered a successful approach to overcome 'the morphine effect'. 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 9 pre-defined time points within the first 6 hours following oral intake of the ticagrelor loading dose. 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. 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.
Sections du résumé
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 coadministration 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 9 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.
Identifiants
pubmed: 32207836
pii: VM/OJS/J/65876
doi: 10.5603/CJ.a2020.0040
pmc: PMC9170314
doi:
Substances chimiques
Narcotics
0
Platelet Aggregation Inhibitors
0
Purinergic P2Y Receptor Antagonists
0
Naloxone
36B82AMQ7N
Morphine
76I7G6D29C
Ticagrelor
GLH0314RVC
Types de publication
Clinical Trial
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
432-440Références
Eur Heart J. 2016 Jan 14;37(3):245-52
pubmed: 26491112
Eur J Clin Invest. 2016 Jan;46(1):7-14
pubmed: 26449338
Lancet. 2010 Jan 23;375(9711):283-93
pubmed: 20079528
Catheter Cardiovasc Interv. 2013 Jul 1;82(1):E1-27
pubmed: 23299937
Int J Clin Pharmacol Ther. 2012 May;50(5):360-7
pubmed: 22541841
Int J Cardiol. 2016 Jul 15;215:201-8
pubmed: 27128531
Cardiol J. 2018;25(3):291-300
pubmed: 29671864
Palliat Med. 1996 Apr;10(2):135-44
pubmed: 8800821
Neurogastroenterol Motil. 2004 Oct;16 Suppl 2:46-53
pubmed: 15357851
J Am Coll Cardiol. 2012 Aug 14;60(7):645-81
pubmed: 22809746
Eur Heart J. 2018 Jan 7;39(2):119-177
pubmed: 28886621
J Am Coll Cardiol. 2016 May 3;67(17):1994-2004
pubmed: 27012781
Eur Heart J. 2016 Jan 14;37(3):267-315
pubmed: 26320110
Thromb Haemost. 2017 Apr 3;117(4):727-733
pubmed: 28150850
J Am Coll Cardiol. 2015 Feb 10;65(5):511-2
pubmed: 25660931
Am Heart J. 2005 Jun;149(6):1043-9
pubmed: 15976786
J Am Coll Cardiol. 2014 Feb 25;63(7):630-635
pubmed: 24315907
Thromb Res. 2017 Jan;149:88-94
pubmed: 27773347
J Interv Cardiol. 2009 Aug;22(4):385-9
pubmed: 19496900
Thromb Haemost. 2017 Apr 3;117(4):718-726
pubmed: 28203684
J Pain Symptom Manage. 2002 Jul;24(1):71-90
pubmed: 12183097
Thromb Haemost. 2018 Dec;118(12):2126-2133
pubmed: 30453344
Circ Cardiovasc Interv. 2014 Dec 31;8(1):
pubmed: 25552565