title: Methods to evaluate the pharmacology of oral antiplatelet drugs.
abstract: Principally, there are two reasons why the pharmacological response to antiplatelet drugs should be measured: on the one hand, an insufficient inhibition of platelet function may result in atherothrombotic complications; on the other hand, an excessive inhibition of platelet function may lead to bleeding complications. The clinical importance to measure the effects of antiplatelet drugs is demonstrated by increasingly growing evidence for an association of resistance to antiplatelet drugs with thromboembolic events. It is often claimed that there is no generally accepted definition of "resistance" and, instead, there is an ongoing semantic discussion about the correct term to be used to describe this phenomenon. From the pharmacological point of view, there is only one acceptable definition of "resistance" to antiplatelet drugs: the term "resistance" should be used when a drug is unable to hit its pharmacological target. Thus, laboratory methods used to evaluate the effects of antiplatelet drugs should be designed to measure the direct pharmacodynamic effect of a drug, rather than the consequences for global platelet function. Based on physiological/pathophysiological, pharmacological, and practical considerations, the authors propose the following assays to be used to measure the effects of oral antiplatelet drugs: for the detection of aspirin actions, thromboxane or arachidonic acid-induced responses (light aggregometry, whole-blood aggregometry) should be measured; for the detection of clopidogrel actions, VASP (vasodilator-stimulated phosphoprotein) phosphorylation (flow cytometry) or ADP-(adenosine diphosphate-)induced responses (light aggregometry, whole-blood aggregometry, possibly also flow cytometry) should be measured.
authors.affiliation: Institute of Pharmacology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany. artur.weber@uk-essen.de
authors.forename: Artur-Aron
authors.initials: AA
authors.lastname: Weber
authors.forename: Michael
authors.initials: M
authors.lastname: Adamzik
authors.forename: Hagen S
authors.initials: HS
authors.lastname: Bachmann
authors.forename: Klaus
authors.initials: K
authors.lastname: Görlinger
authors.forename: Maria
authors.initials: M
authors.lastname: Grandoch
authors.forename: Kirsten
authors.initials: K
authors.lastname: Leineweber
authors.forename: Hannes
authors.initials: H
authors.lastname: Müller-Beissenhirtz
authors.forename: Folker
authors.initials: F
authors.lastname: Wenzel
authors.forename: Christoph
authors.initials: C
authors.lastname: Naber
mesh_terms: D000284:Administration, Oral; D015906:Angioplasty, Balloon, Coronary / Q000009:adverse effects*; D001681:Biological Assay / Q000379:methods*; D001807:Blood Vessel Prosthesis / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004341:Drug Evaluation / Q000379:methods*; D006331:Heart Diseases / Q000209:etiology / Q000517:prevention & control*; D006801:Humans; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects*; D010818:Practice Patterns, Physicians' / Q000639:trends; D015607:Stents / Q000009:adverse effects; D013927:Thrombosis / Q000209:etiology / Q000517:prevention & control*
chemical_list: D010975:Platelet Aggregation Inhibitors