HALOFENATE - POTENT INHIBITOR OF NORMAL AND HYPERSENSITIVE PLATELETS

Abstract

The effects of incubating, halofenate were studied with both normal platelets and platelets made hypersensitive in vitro by incorporation of 55% excess cholesterol into their membranes. At therapeutic concentrations, halofenate caused a time- and dose-dependent inhibition of the aggregation of normal platelets by epinephrine. After 30 min incubation at 37.degree. C, halofenate significantly inhibited the extent of aggregation by 88% (P < 0.01), whereas clofibrate inhibited aggregation by 44% (P < 0.01). Halofenate was a more potent inhibitor of platelets than clofibrate (P < 0.01). The mean threshold concentration of epinephrine necessary for aggregation of normal platelets (4.2 .mu.M) was not significantly increased with clofibrate (10 .mu.M) but was markedly elevated with halofenate (245 .mu.M, P < 0.001). Significant but less dramatic increases in threshold concentration of ADP and collagen were found with halofenate but not clofibrate. Cholesterol-rich platelets were 114-fold more sensitive to epinephrine and 2-fold more sensitive to ADP than normal platelets but after incubation with halofenate became even less sensitive than normal. Clofibrate inhibited the extent of aggregation of hypersensitive platelets but did not alter the threshold concentration of epinephrine necessary for aggregation. Halofenate is more potent than clofibrate in reducing the sensitivity of normal platelets to aggregating agents in vitro and can completely reverse experimentally produced platelet hypersensitivity. Halofenate might be useful in reversing increased platelet sensitivity in cardiovascular diseases.