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Thromboxane Synthase Activity and Platelet Function After Furegrelate Administration in Man
Author(s) -
Mohrland J. Scott,
Lugt J. T. Vander,
Gorman R. R.,
Lakings D. B.
Publication year - 1989
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1002/j.1552-4604.1989.tb03237.x
Subject(s) - thromboxane a synthase , ex vivo , platelet , thromboxane a2 , chemistry , thromboxane , thromboxane b2 , in vivo , urine , endocrinology , medicine , oral administration , pharmacology , biochemistry , in vitro , biology , microbiology and biotechnology
Furegrelate sodium (U‐63,557A), a pyridine‐derivative thromboxane synthase inhibitor, was administered orally in single doses of 200 to 1600 mg to normal male subjects. Furegrelate produced a dose‐related inhibition of thromboxane synthesis for 8–12 hours when measured either ex vivo from platelet‐rich plasma (PRP) or in vivo from urine. In general, the extent of thromboxane synthesis inhibition was greater in PRP than in urine. Furegrelate significantly inhibited platelet aggregation, but the effect was variable and measurements of thromboxane synthase did not predict the impact on platelet aggregation. Bleeding times and coagulation parameters were not altered significantly. Furegrelate was well absorbed orally with T max = 1 hr and t ½ = 3.5 to 5 hrs. There was no marked metabolism; elimination was primarily by renal excretion of parent compound. Thus, furegrelate is an effective inhibitor of thromboxane synthase in man with a relatively long biologic and circulating half‐life.