INHIBITION OF THROMBOXANE BIOSYNTHESIS AND PLATELET-FUNCTION BY INDOBUFEN IN TYPE-II DIABETES-MELLITUS

Indobufen is a reversible inhibitor of platelet prostaglandin G/H-synt hase. To verify the dose dependence of the antiplatelet effect of indo bufen on ex vivo and in vivo indexes of thromboxane (TX) biosynthesis and TXA2-dependent platelet function, we studied nine patients with no n-insulin-dependent diabetes mellitus (NIDDM). This was a randomized, double-blind, crossover study in which each patient was treated with t hree different daily regimens (50 mg BID, 100 mg BID, and 200 mg BID) of indobufen for 1 week, with a 7-day washout period between treatment s. Urinary 11-dehydro-TXB2 excretion averaged 58.2+/-21.8 ng/h at base line. TX metabolite excretion was reduced dose dependently by indobufe n: by 67% at 50 mg BID, 72% at 100 mg BID, and 81% at 200 mg BID. Plat elet cyclooxygenase activity, ATP release, collagen-induced platelet a ggregation, and bleeding time also were modified dose dependently by i ndobufen. Biochemical demonstration of suppressed platelet TXA2 in viv o was accompanied by evidence of inhibited platelet function as assess ed ex vivo. Under pathophysiological conditions, such as NIDDM, which are associated with enhanced TXA2 synthesis, more than 95% suppression of platelet cyclooxygenase activity may be necessary to produce virtu ally maximal inhibition of platelet TXA2 biosynthesis in vivo.