Effect of ibuprofen on platelet function in normal subjects and hemophiliac patients

Abstract

New propionic acid derivatives are claimed to induce a lower incidence of gastrointestinal bleeding and hemostatic disturbance than older anti-inflammatory analgesics such as aspirin. One of these (ibuprofen, Motrin) was given (600 mg orally) to normal subjects and hemophiliac subjects on a random, double-blind basis (lactose placebo). Platelet adhesiveness, aggregation, platelet and red cell counts, percent packed cells, percent hemoglobin, serum ibuprofen levels, and modified Ivy bleeding time were measured before and 2 and 24 hr after drug. Predrug and 24-hr postdrug values were normal, but at 2 hr after drug, adenosine diphosphate, epinephrine, and collagen aggregations were inhibited and bleeding times were slightly but significantly prolonged in the ibuprofen-treated normal subjects. The other parameters tested remained unchanged. Similar results were obtained in the ibuprofen-treated hemophiliac patients, although bleeding time was not prolonged. The results suggest that ibuprofen may be given to hemophiliac subjects with greater safety than some of the older anti-inflammatory drugs.

Ibuprofen protects platelet cyclooxygenase from irreversible inhibition by aspirin.

“…27 Twenty-four hours after ingesting ibuprofen, however, the effects of the drug on platelet function and prostaglandin synthesis had disapeared. 12 The response of platelets to aggregating agents, including arachidonate, was similar to the reaction of control platelets. No differences in the generation of thromboxane B 2 or the secretion measured on the lumiaggregometer could be identified in ibuprofen compared to untreated platelet samples.…”

“…11 In contrast to aspirin, however, the action of ibuprofen is short-lived. 12 Concentrations of the drug, which block conversion of arachidonic acid completely and inhibit platelet response to agonists shortly after ingestion, completely lose their influence within 24 hours.…”

“…12 Investigations into its mechanism of action several years ago 3 " 5 suggested that it suppressed conversion of arachidonic acid by acetylating the enzyme cyclooxygenase. Other potent inhibitors of prostaglandin formation, however, are incapable of acetylating proteins and must block cyclooxygenase in some other manner.…”

“…11 Unlike aspirin, the effect of ibuprofen on platelet cyclooxygenase is short-lived, and platelets are no longer affected 24 hours after administration of the drug in vivo. 12 Studies in vitro suggest that the agent may compete with aspirin for the active site on the enzyme. 14 The reported differences between the effects of aspirin and ibuprofen suggested that in vivo studies might help to clarify the mechanism or mechanisms by which the different agents inhibit prostaglandin synthesis.…”

Effect of tenidap sodium on the pharmacodynamics and plasma protein binding of warfarin in healthy volunteers.

“…Non-steroidal anti-inflammatory drugs (NSAIDs) also inhibit cyclo-oxygenase; these include salicylates [10], ibuprofen [11][12][13], phenylbutazone [14] and flurbiprofen [15, 16], which have all been shown to interact with warfarin, and these interactions may be of clinical importance [14]. Interactions may occur through a number of different mechanisms, including displacement of warfarin (which is highly plasma protein bound) from plasma protein binding sites, and stereoselective inhibition of the metabolism of the Sisomer of warfarin [14,17].…”