PMID- 22747575
OWN - NLM
STAT- MEDLINE
DCOM- 20130418
LR  - 20181202
IS  - 1365-2710 (Electronic)
IS  - 0269-4727 (Linking)
VI  - 37
IP  - 6
DP  - 2012 Dec
TI  - Lack of clinically significant pharmacological interactions between ticagrelor 
      and enoxaparin or unfractionated heparin in healthy subjects.
PG  - 704-11
LID - 10.1111/j.1365-2710.2012.01367.x [doi]
AB  - WHAT IS KNOWN AND 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). WHAT IS NEW AND 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.
CI  - (c) 2012 Blackwell Publishing Ltd.
FAU - Teng, R
AU  - Teng R
AD  - Department of Clinical Pharmacology, AstraZeneca LP, Wilmington, DE, USA. 
      renli.teng@astrazeneca.com
FAU - Butler, K
AU  - Butler K
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20120702
PL  - England
TA  - J Clin Pharm Ther
JT  - Journal of clinical pharmacy and therapeutics
JID - 8704308
RN  - 0 (Anticoagulants)
RN  - 0 (Enoxaparin)
RN  - 0 (Platelet Aggregation Inhibitors)
RN  - 0 (Purinergic P2Y Receptor Antagonists)
RN  - 9005-49-6 (Heparin)
RN  - GLH0314RVC (Ticagrelor)
RN  - K72T3FS567 (Adenosine)
SB  - IM
MH  - Adenosine/adverse effects/*analogs & derivatives/pharmacokinetics/pharmacology
MH  - Adult
MH  - Anticoagulants/adverse effects/*pharmacology
MH  - Blood Coagulation Tests
MH  - Cross-Over Studies
MH  - Drug Interactions
MH  - Enoxaparin/adverse effects/*pharmacology
MH  - Female
MH  - Heparin/adverse effects/*pharmacology
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Platelet Aggregation/drug effects
MH  - Platelet Aggregation Inhibitors/adverse effects/pharmacokinetics/pharmacology
MH  - Purinergic P2Y Receptor Antagonists/adverse effects/pharmacokinetics/pharmacology
MH  - Ticagrelor
MH  - Young Adult
EDAT- 2012/07/04 06:00
MHDA- 2013/04/20 06:00
CRDT- 2012/07/04 06:00
PHST- 2012/07/04 06:00 [entrez]
PHST- 2012/07/04 06:00 [pubmed]
PHST- 2013/04/20 06:00 [medline]
AID - 10.1111/j.1365-2710.2012.01367.x [doi]
PST - ppublish
SO  - J Clin Pharm Ther. 2012 Dec;37(6):704-11. doi: 10.1111/j.1365-2710.2012.01367.x. 
      Epub 2012 Jul 2.