ticagrelor and methylnaltrexone

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).

Topics: Administration, Intravenous; Administration, Oral; Aged; Analgesics, Opioid; Blood Platelets; Cell Adhesion Molecules; Coronary Artery Disease; Cross-Over Studies; Double-Blind Method; Drug Interactions; Female; Florida; Gastric Emptying; Gastrointestinal Absorption; Humans; Male; Microfilament Proteins; Middle Aged; Morphine; Naltrexone; Narcotic Antagonists; Phosphoproteins; Platelet Aggregation; Platelet Aggregation Inhibitors; Prospective Studies; Quaternary Ammonium Compounds; Ticagrelor; Treatment Outcome

Topics: Analgesics, Opioid; Coronary Artery Disease; Humans; Morphine; Naltrexone; Quaternary Ammonium Compounds; Ticagrelor; Treatment Outcome