title: Effect of aspirin infusions on platelet function in humans.
abstract: 1. The inhibitory effects of aspirin on platelet function in vitro have been shown to be both time (over 3 h) and concentration (1-10 mumol/l) dependent. 2. To determine if these effects occurred in vivo, four volunteers received intravenous infusions on four occasions, to give constant plasma aspirin concentrations of 0, 1, 2 and 4 mumol/l over 3 h. Infusions were performed at intervals of at least 2 weeks. 3. Before and during the infusions, blood was taken for assay of aspirin concentrations, and measurements of platelet aggregation in response to collagen, adenosine 5'-pyrophosphate and arachidonate. Thromboxane generation after stimulated platelet aggregation and whole-blood coagulation was also measured. 4. At each aspirin concentration, both platelet aggregation and thromboxane generation in response to collagen and arachidonate were inhibited progressively over the 3 h infusion period. Greatest inhibition was seen during the 4 mumol/l infusion, which produced maximal or near-maximal inhibition by the third hour. 5. Thromboxane generated during whole-blood coagulation was similarly inhibited in both a time- and concentration-dependent manner throughout all aspirin infusions. 6. The progressive nature of the inhibition of platelet function with these low aspirin concentrations may be due to either slow aspirin transport across the platelet membrane or delayed interaction with cyclo-oxygenase.
authors.affiliation: Department of Clinical and Experimental Pharmacology, University of Adelaide, Australia.
authors.forename: K M
authors.initials: KM
authors.lastname: Wilson
authors.forename: D M
authors.initials: DM
authors.lastname: Siebert
authors.forename: E M
authors.initials: EM
authors.lastname: Duncan
authors.forename: A A
authors.initials: AA
authors.lastname: Somogyi
authors.forename: J V
authors.initials: JV
authors.lastname: Lloyd
authors.forename: F
authors.initials: F
authors.lastname: Bochner
mesh_terms: D000244:Adenosine Diphosphate / Q000494:pharmacology; D000328:Adult; D001095:Arachidonic Acids / Q000494:pharmacology; D001241:Aspirin / Q000097:blood / Q000494:pharmacology*; D003094:Collagen / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010974:Platelet Aggregation / Q000187:drug effects*; D013928:Thromboxane A2 / Q000097:blood; D013929:Thromboxane B2 / Q000097:blood; D013997:Time Factors
chemical_list: D001095:Arachidonic Acids; D013929:Thromboxane B2; D013928:Thromboxane A2; D000244:Adenosine Diphosphate; D003094:Collagen; D001241:Aspirin