Download PDF
Thromb Haemost 1976; 35(02): 358-363
DOI: 10.1055/s-0038-1647929
Original Article
Schattauer GmbH

The Effect of Halofenate or Halofenate Free Acid on Human, Rat and Guinea Pig Platelet Aggregation

D.H Minsker
1   Merck Institute for Therapeutic Research, West Point, Pennsylvania 19486, USA
,
P.T Jordan
1   Merck Institute for Therapeutic Research, West Point, Pennsylvania 19486, USA
,
P Kling
1   Merck Institute for Therapeutic Research, West Point, Pennsylvania 19486, USA
,
A MacMillan
1   Merck Institute for Therapeutic Research, West Point, Pennsylvania 19486, USA
,
H.B Hucker
1   Merck Institute for Therapeutic Research, West Point, Pennsylvania 19486, USA
,
D.J Tocco
1   Merck Institute for Therapeutic Research, West Point, Pennsylvania 19486, USA
› Author Affiliations
Further Information

Publication History

Received 10 April 1975

Accepted 28 July 1975

Publication Date:
02 July 2018 (online)

Also available at
    Permissions and Reprints

Summary

Halofenate free acid (HFA), the major metabolite of the hypolipemic agent halofenate, blocked the secondary phase of human platelet aggregation induced by ADP, epinephrine, or thrombin; higher concentrations of clohbrate free acid (CFA) were required to produce similar inhibitory effects on platelet aggregation. HFA and CFA inhibited collagen-induced aggregation of human, rat, or guinea pig platelets. Halofenate orally administered to rats caused inhibition of collagen-induced aggregation when plasma levels of HFA exceeded 300 μg/ml, a clinically achievable human plasma concentration. The platelet inhibitory effects of clofibrate administration were less than those observed with halofenate administration.

 

  • References

  • 1 Bluhm G. B, Riddle J. M. 1973 Seminars in Arthritis and Rheumatism. 2, 355.
    PubMedSearch in Google Scholar
  • 2 Born G. V. R. 1962; Quantitative investigations into the aggregation of blood platelets. Journal of Physiology 162: 67 P.
    PubMedSearch in Google Scholar
  • 3 Fanelli G. M, Bohn D. L, Reilly S. S, Baer J. E. 1972; Renal excretion and uricosuric properties of halofenate, a hypolipidemicuricosuric agent, in the chimpanzee. Journal of Pharmacology and Experimental Therapeutics 180: 377.
    PubMedSearch in Google Scholar
  • 4 Gilfillan J. L, Hunt V. M, Huff J. W. 1971; The hypolipemic properties of 2-acetoamidoethyl (p-chlorophenyl)(m-trifluoromethylphenoxy)acetate in the rat (35474). Proceedings of the Society of Experimental Biology and Medicine 136: 1274.
    PubMedSearch in Google Scholar
  • 5 Hucker H. B, Grady L. T, Michniewicz B. M, Stauffer S. C, White S. E, Maha G. E, McMahon F. G. 1971; Metabolism of a new hypolipidemic agent, 2-acetomidoethyl(p-chloro-phenyl)(m-trifluoromethylphenoxy)-acetate (halofenate) in the rat, dog, Rhesus monkey and man. Journal of Pharmacology and Experimental Therapeutics 179: 359.
    PubMedSearch in Google Scholar
  • 6 Hutchison J. C, Wilkinson W. H. 1973; The uricosuric action of halofenate (MK-185) in patients with hyperuricemia or uncomplicated primary gout and hyperlipidemia. Atherosclerosis 18: 353.
    CrossrefPubMedSearch in Google Scholar
  • 7 Sirtori C, Hurwitz A, Sabih K, Azarnoff D. L. 1972; Clinical evaluation of MK-185: a new hypolipidemic drug. Lipids 7: 96.
    CrossrefPubMedSearch in Google Scholar