Lack of clinically significant pharmacological interactions between ticagrelor and enoxaparin or unfractionated heparin in healthy subjects.
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 m...
| Publicado en: | Journal of Clinical Pharmacy & Therapeutics Vol. 37; no. 6; pp. 704 - 712 |
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| Autores principales: | , |
| Formato: | research tables/charts Journal Article |
| Publicado: |
Wiley-Blackwell
Dec2012
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=104430875&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 104430875 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 02694727 EV4 jtl: Journal of Clinical Pharmacy & Therapeutics issn: 02694727 maglogo: Y pubinfo: dt: Dec2012 vid: 37 iid: 6 pid: 480 pub: Wiley-Blackwell place: Malden, Massachusetts artinfo: ui: 104430875 83005582 10.1111/j.1365-2710.2012.01367.x NLM22747575 104430875 ppf: 704 ppct: 8 formats: fmt: @attributes: type: P tig: atl: Lack of clinically significant pharmacological interactions between ticagrelor and enoxaparin or unfractionated heparin in healthy subjects. aug: au: Teng, R. Butler, K. affil: Department of Clinical Pharmacology, AstraZeneca LP, Wilmington, DE, USA sug: subj: Acute Coronary Syndrome Prevention and Control Platelet Aggregation Inhibitors Therapeutic Use Heparin, Low-Molecular-Weight Pharmacodynamics Adenosine Analogs and Derivatives Drug Interactions Evaluation Adenosine Pharmacokinetics Adenosine Pharmacodynamics Human Crossover Design Random Assignment Descriptive Statistics Confidence Intervals Male Female Data Analysis Software Analysis of Variance Adult Young Adult Middle Age Funding Source Adult: 19-44 years Middle Aged: 45-64 years Male Female 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 IPAmax (−3·8%; 94·6%, 91·0%) and AUEC2-12 (−6·8%; 888·6%.h, 828·3%.h) vs. ticagrelor alone (95% CI: final extent IPAmax−5·7%, −1·6%; AUEC2-12−109·8%.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. pubtype: Academic Journal doctype: research tables/charts Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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