title: Lack of clinically significant pharmacological interactions between ticagrelor and enoxaparin or unfractionated heparin in healthy subjects.
abstract: OBJECTIVE
  Patients with acute coronary syndromes (ACS) receive several pharmacological therapies concomitantly, including antiplatelet and anticoagulant agents. As unfractionated heparin (UFH) activates platelets in vitro and in vivo, co-administration with an antiplatelet agent may lead to decreased clinical effectiveness of the latter. The aim was therefore to determine any potential drug-drug interactions between the new oral antiplatelet agent ticagrelor, and UFH or enoxaparin.
  
  
  METHODS
  In two open-label, three-period, crossover trials, healthy subjects were randomized to receive ticagrelor alone or with enoxaparin (study 1) or UFH (study 2), or enoxaparin or UFH alone. Ticagrelor plasma concentrations, inhibition of platelet aggregation (IPA), anti-factor Xa levels, activated partial thromboplastin time (aPTT) and activated coagulation time (ACT) were measured.
  
  
  RESULTS
  Thirty and 28 subjects completed studies 1 and 2, respectively. Study drugs were generally well tolerated, with no significant bleeding or serious adverse events. Co-administration with enoxaparin or UFH had no significant effect on ticagrelor pharmacokinetics. The effect of ticagrelor on IPA was unimpaired by co-administration of enoxaparin, except for a marginal (-2.9%; 908.7%.h, 881.9%.h) reduction in final extent area under the effect curve (AUEC)(2-12) (95% CI: -51.6%.h, -2.0%.h). Co-administering UFH with ticagrelor caused small decreases in IPA(max) (-3.8%; 94.6%, 91.0%) and AUEC(2-12) (-6.8%; 888.6%.h, 828.3%.h) vs. ticagrelor alone (95% CI: final extent IPA(max) -5.7%, -1.6%; AUEC(2-12) -109.8%.h, -10.8%.h). Ticagrelor had no clinically significant effects on enoxaparin as assessed by anti-factor Xa (study 1), or UFH as assessed by aPTT or ACT (study 2).
  
  
  CONCLUSIONS
  Enoxaparin and UFH had no effect on the pharmacokinetics and no clinically significant effect on the pharmacodynamics of ticagrelor. Ticagrelor had no clinically significant effects on the pharmacodynamics of enoxaparin or UFH.
authors: Department of Clinical Pharmacology, AstraZeneca LP, Wilmington, DE, USA. renli.teng@astrazeneca.com
authors: R
authors: R
authors: Teng
authors: K
authors: K
authors: Butler
mesh_terms: D000241:Adenosine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology; D000328:Adult; D000925:Anticoagulants / Q000009:adverse effects / Q000494:pharmacology*; D001780:Blood Coagulation Tests; D018592:Cross-Over Studies; D004347:Drug Interactions; D017984:Enoxaparin / Q000009:adverse effects / Q000494:pharmacology*; D005260:Female; D006493:Heparin / Q000009:adverse effects / Q000494:pharmacology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology; D058921:Purinergic P2Y Receptor Antagonists / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology; D000077486:Ticagrelor; D055815:Young Adult
chemical_list: D000925:Anticoagulants; D017984:Enoxaparin; D010975:Platelet Aggregation Inhibitors; D058921:Purinergic P2Y Receptor Antagonists; D006493:Heparin; D000077486:Ticagrelor; D000241:Adenosine