Effect of etofylline clofibrate on experimental thrombus formation and prostacyclin activation

1-(7-Theophyllinyl)-2-ethyl-[2-(p-chlorophenoxy)-isobutyrate] (etofylline clofibrate, theofibrate, Duolip) was shown to possess substantial thrombus disaggregating activity in the microcirculation of the hamster cheek pouch following minor vascular damage by electrical stimulation. At 12 mg/kg p.o. the moderate effect of a single dose (12% reduction in disaggregation time) increased to a maximum reduction of 31 and 43% following 5 and 7 consecutive daily applications, respectively. Etofylline clofibrate was more active than other drugs already tested in this test system, but less than the prostaglandins PGE1 and PGI2. The antithrombotic efficacy found in both in vivo tests, thrombus formation and disaggregation, suggests as mode of action of etofylline clofibrate an agonistic interaction with intimal PGI2. This could be by enhancement of its production or by a synergistic interaction with this prostanoid, rather than inhibition of thromboxane A2 synthetase.