Effects of repeated oral doses of fenflumizole on platelet aggregation and thromboxane formation in man ex vivo.
Anti-platelet effects of fenflumizole, a new cyclo-oxygenase inhibitor, were studied in man ex vivo. Fenflumizole was given to male volunteers at the oral doses of 25, 50 or 100 mg per day, each dose for a period of seven days. The formation of thromboxane B2 (TXB2) during whole blood clotting, platelet aggregation induced by arachidonic acid and ADP, the formation of TXB2 during aggregation as well as serum concentration of fenflumizole were measured repeatedly during drug administration and for a fortnight after drug discontinuation. TXB2 formation during whole blood clotting was decreased dose-dependently by fenflumizole. The degree of inhibition of TXB2 formation was proportional to fenflumizole concentration in serum within each individual. The lag phase of platelet aggregation induced by arachidonic acid was prolonged and the formation of TXB2 during aggregation decreased by fenflumizole. No total inhibition of either TXB2 synthesis or platelet aggregation was caused by the fenflumizole doses used. The results show that the degree of inhibition of platelet thromboxane forming capacity by repeated doses of fenflumizole is closely related to the concentration of the drug in blood. Platelet aggregation however is less sensitive to changes in fenflumizole levels and cannot be assessed solely on the basis of cyclo-oxygenase activity.
Dahl-Puustinen
M L
ML
Department of Physiology, University of Turku, Finland.
Corell
T
T
Koch
K
K
Puustinen
T
T
D015121:6-Ketoprostaglandin F1 alpha / Q000096:biosynthesis; D000284:Administration, Oral; D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D007093:Imidazoles / Q000009:adverse effects / Q000097:blood / Q000494:pharmacology*; D008297:Male; D010974:Platelet Aggregation / Q000187:drug effects*; D013929:Thromboxane B2 / Q000096:biosynthesis*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D007093:Imidazoles; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; C038996:fenflumizole