PLATELET-FUNCTION IN HEALTHY-VOLUNTEERS G IVEN 50 MG ACETYLSALICYLIC-ACID DAILY

The antithrombotic effect of acetylsalicylic acid (ASS) is attributed in part to its inhibitory action on platelet cyclooxygenase and, there by, thromboxane A(2) (TXA(2)) formation. The therapeutic goal of low-d ose ASS regimens was the development of a preparation showing a high i nhibitory capacity on platelet TXA(2) generation whilst leaving vascul ar prostaglandin 12 (PGI(2)) synthesis unaffected, thereby minimizing side effects. The effect of a new acid-resistant preparation of 50 mg ASS (Thrombo-ASS 50 mg(R)) on plasma levels of ASS, salicylate, TXB(2) , 11-dehydro-thromboxane B-2, serum thromboxane B-2 and malonyl dialde hyde, the conversion of exogenous C-14-arachidonic acid to TXB(2) and hydroxy-5,8,10-heptadecatrienoic acid (HHT), as well as on the urinary metabolites 2,3-dinor-6-oxo-PGF(1 alpha) and 2,3-diner TXB(2), were c ompared in a crossover trial to those of a marketed preparation (Aspir in 100 mg(R)) in healthy volunteers after a single dose and repeated a dministration of ASS. While platelet activity was inhibited by both th e test and the reference substance to a comparable extent, vascular PG I(2) production (as determined by urinary 2,3-dinor-6-oxo-PGF(1 alpha) excretion) was less affected by the test substance. These findings co nfirm the claim that a dosage of 50 mg ASS administered daily as an en teric coated or uncoated tablet is sufficient to almost completely blo ck platelet cyclooxygenase, while the respective vascular enzyme is on ly minimally affected.