Effects of Methylnaltrexone on Ticagrelor-Induced Antiplatelet Effects in Coronary Artery Disease Patients Treated With Morphine.
Administration, Intravenous
Administration, Oral
Aged
Analgesics, Opioid
/ administration & dosage
Blood Platelets
/ drug effects
Cell Adhesion Molecules
/ blood
Coronary Artery Disease
/ blood
Cross-Over Studies
Double-Blind Method
Drug Interactions
Female
Florida
Gastric Emptying
/ drug effects
Gastrointestinal Absorption
/ drug effects
Humans
Male
Microfilament Proteins
/ blood
Middle Aged
Morphine
/ administration & dosage
Naltrexone
/ administration & dosage
Narcotic Antagonists
/ administration & dosage
Phosphoproteins
/ blood
Platelet Aggregation
/ drug effects
Platelet Aggregation Inhibitors
/ administration & dosage
Prospective Studies
Quaternary Ammonium Compounds
/ administration & dosage
Ticagrelor
/ administration & dosage
Treatment Outcome
methylnaltrexone
morphine
pharmacodynamic
pharmacokinetic
ticagrelor
Journal
JACC. Cardiovascular interventions
ISSN: 1876-7605
Titre abrégé: JACC Cardiovasc Interv
Pays: United States
ID NLM: 101467004
Informations de publication
Date de publication:
26 08 2019
26 08 2019
Historique:
received:
01
03
2019
revised:
17
05
2019
accepted:
20
05
2019
pubmed:
5
8
2019
medline:
2
9
2020
entrez:
5
8
2019
Statut:
ppublish
Résumé
The aim of this study was to assess if intravenous methylnaltrexone can counteract the effects of morphine on the pharmacokinetic (PK) and pharmacodynamic (PD) profiles of ticagrelor. Morphine delays the onset of action of oral P2Y In this prospective, randomized, double-blind, placebo-controlled, crossover study, aspirin-treated patients with stable coronary artery disease (n = 30) were randomized to receive methylnaltrexone (0.3 mg/kg intravenous) or matching placebo. After methylnaltrexone or placebo administration, all patients received morphine (5 mg intravenous). This was followed 15 min later by a 180-mg loading dose of ticagrelor. Patients crossed over to the alternative study treatment after 7 ± 2 days of washout. PK and PD assessments were performed at 12 time points (6 pre- and 6 post-crossover). PK analysis included measurement of plasma levels of ticagrelor and its major active metabolite (AR-C124910XX). PD assessments included VerifyNow P2Y Only marginal changes in plasma levels of ticagrelor (and its major active metabolite) were observed with ticagrelor: maximum plasma concentration and area under the plasma concentration versus time curve from time 0 to the last measurable concentration were 38% and 30% higher, respectively, in patients receiving methylnaltrexone compared with those receiving placebo, but no differences in time to maximum plasma concentration were observed. There were no differences in P2Y In patients with coronary artery disease receiving morphine, intravenous administration of the peripheral opioid receptor antagonist methylnaltrexone leads to only marginal changes in plasma levels of ticagrelor and its major metabolite, without affecting levels of platelet reactivity. (Effect of Methylnaltrexone on the PK/PD Profiles of Ticagrelor in Patients Treated With Morphine; NCT02403830).
Sections du résumé
OBJECTIVES
The aim of this study was to assess if intravenous methylnaltrexone can counteract the effects of morphine on the pharmacokinetic (PK) and pharmacodynamic (PD) profiles of ticagrelor.
BACKGROUND
Morphine delays the onset of action of oral P2Y
METHODS
In this prospective, randomized, double-blind, placebo-controlled, crossover study, aspirin-treated patients with stable coronary artery disease (n = 30) were randomized to receive methylnaltrexone (0.3 mg/kg intravenous) or matching placebo. After methylnaltrexone or placebo administration, all patients received morphine (5 mg intravenous). This was followed 15 min later by a 180-mg loading dose of ticagrelor. Patients crossed over to the alternative study treatment after 7 ± 2 days of washout. PK and PD assessments were performed at 12 time points (6 pre- and 6 post-crossover). PK analysis included measurement of plasma levels of ticagrelor and its major active metabolite (AR-C124910XX). PD assessments included VerifyNow P2Y
RESULTS
Only marginal changes in plasma levels of ticagrelor (and its major active metabolite) were observed with ticagrelor: maximum plasma concentration and area under the plasma concentration versus time curve from time 0 to the last measurable concentration were 38% and 30% higher, respectively, in patients receiving methylnaltrexone compared with those receiving placebo, but no differences in time to maximum plasma concentration were observed. There were no differences in P2Y
CONCLUSIONS
In patients with coronary artery disease receiving morphine, intravenous administration of the peripheral opioid receptor antagonist methylnaltrexone leads to only marginal changes in plasma levels of ticagrelor and its major metabolite, without affecting levels of platelet reactivity. (Effect of Methylnaltrexone on the PK/PD Profiles of Ticagrelor in Patients Treated With Morphine; NCT02403830).
Identifiants
pubmed: 31377269
pii: S1936-8798(19)31216-6
doi: 10.1016/j.jcin.2019.05.028
pii:
doi:
Substances chimiques
Analgesics, Opioid
0
Cell Adhesion Molecules
0
Microfilament Proteins
0
Narcotic Antagonists
0
Phosphoproteins
0
Platelet Aggregation Inhibitors
0
Quaternary Ammonium Compounds
0
vasodilator-stimulated phosphoprotein
0
methylnaltrexone
0RK7M7IABE
Naltrexone
5S6W795CQM
Morphine
76I7G6D29C
Ticagrelor
GLH0314RVC
Banques de données
ClinicalTrials.gov
['NCT02403830']
Types de publication
Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1538-1549Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.