Abstract 19115: Effect of the Peripheral Opioid Receptor Antagonist Methylnaltrexone on the Pharmacokinetic and Pharmacodynamic Profiles of Ticagrelor in Patients Receiving Morphine: A Prospective Randomized Placebo-Controlled Trial
Introduction: Morphine causes delayed onset of action of ticagrelor by inhibiting gastric emptying and leading to delayed drug absorption. Methylnaltrexone (MNT) is a peripheral opioid receptor antagonist which has the potential to prevent opioid-induced peripherally mediated side effects, such as gastric emptying inhibition, without affecting analgesia. If intravenous (iv) MNT can counteract the effects of morphine on the pharmacokinetic (PK) and pharmacodynamic (PD) profiles of ticagrelor is unknown and represented the aim of this study.
Methods: In this prospective, randomized, double-blind, placebo-controlled, cross-over study, aspirin treated patients with coronary artery disease (CAD) (n=30) were treated with iv MNT (0.3 mg/Kg) or placebo. Immediately after MNT/placebo, patients received iv morphine (5 mg), followed by ticagrelor (180 mg) after 15 min. Patients crossed-over to the alternate study treatment after 7±2 days wash-out. PK/PD assessments were performed at baseline, and 30 min, 1, 2, 4 and 6 h after ticagrelor administration. PK analysis included measurement of plasma levels of ticagrelor and its major active metabolite (AR-C124910XX). PD assessments included VerifyNow P2Y12 (VN), light transmittance aggregometry (LTA) and vasodilator-stimulated phosphoprotein (VASP).
Results: PK analysis showed no significant differences in plasma levels of ticagrelor (Figure, upper panel) and AR-C124910XX (data not shown) between MNT and placebo during the overall study time-course. Accordingly, P2Y12 reaction units (PRU) by VN were similar between MNT and placebo at each time point, including 2-hour (p=0.261; primary end point) (Figure, bottom panel). LTA and VASP showed consistent findings (data not shown).
Conclusions: In CAD patients receiving morphine, iv administration of the peripheral opioid receptor antagonist MNT did not affect ticagrelor’s plasma levels or its platelet inhibitory effects.
Author Disclosures: F. Franchi: None. F. Rollini: None. Y. Park: None. J. Hu: None. M. Kureti: None. J. Rivas: None. J. Mewa: None. G. Faz: None. D. Yaranov: None. L. Been: None. P. Antoun: None. D. Soffer: None. M.M. Zenni: None. T.A. Bass: None. D.J. Angiolillo: Research Grant; Modest; Glaxo-Smith-Kline, Eli Lilly, Daiichi-Sankyo, The Medicines Company, AstraZeneca, Janssen Pharmaceuticals, Inc., Osprey Medical, Inc., Novartis, CSL Behring, and Gilead. Honoraria; Modest; Sanofi, Eli Lilly, Daiichi-Sankyo, The Medicines Company, AstraZeneca, Merck, Abbott Vascular and PLx Pharma. Consultant/Advisory Board; Modest; CeloNova, Johnson & Johnson, and St. Jude Medical.
- © 2016 by American Heart Association, Inc.