ACTION OF HALOFENATE ON PLATELET SHAPE CHANGE AND PROSTAGLANDIN SYNTHESIS

  • 1 January 1978
    • journal article
    • research article
    • Vol. 92  (1) , 45-52
Abstract
HAL [halofenate], a congener of clofibrate, was previously shown to inhibit epinephrine- and ADP-induced platelet aggregation and 14C-serotonin release. The site of action of HAL was investigated by examining platelet shape change, MDA [malondialdehyde] production as a measure of prostaglandin synthesis, and platelet aggregation and MDA production induced by SA [sodium arachidonate]. At the usual maximal therapeutic concentration of HAL (0.96 mM), this drug did not affect the velocity of platelet shape change as measured by a spectrophotometric method. At a higher concentration (3.12 mM), HAL significantly inhibited shape change (P < 0.01). When epinephrine was used to initiate aggregation of PRP [platelet-rich plasma], HAL (0.96 mM) inhibited MDA production over a wide range of epinephrine concentrations (P < 0.01). This was not due to a direct inhibition of prostaglandin formation, since HAL had no effect on SA-induced platelet aggregation or MDA production. Aspirin (4 mM) produced a marked inhibition of MDA production and of platelet aggregation after stimulation with SA. HAL seems to inhibit some step in the platelet reaction prior to the appearance of free arachidonic acid.