Inhibition of Thromboxane Biosynthesis and Platelet Function by Indobufen in Type II Diabetes Mellitus
作者:
G.,
Davi C.,
Patrono I.,
Catalano N.,
Custro C.,
Giammarresi A.,
Ganci F.,
Cosentino A.,
期刊:
Arteriosclerosis and Thrombosis: A Journal of Vascular Biology
(OVID Available online 1993)
卷期:
Volume 13,
issue 9
页码: 1346-1349
ISSN:1049-8834
年代: 1993
出版商: OVID
关键词: thromboxane;diabetes mellitus;indobufen;platelet function;in vivo platelet
数据来源: OVID
摘要:
Indobufen is a reversible inhibitor of platelet prostaglandin G/H-synthase. To verify the dose dependence of the antiplatelet effect of indobufen on ex vivo and in vivo indexes of thromboxane (TX) biosynthesis and TXAj-dependent platelet function, we studied nine patients with non-insulin-dependent diabetes mellitus (NIDDM). This was a randomized, double-blind, crossover study in which each patient was treated with three different daily regimens (50 rag BID, 100 mg BID, and 200 mg BID) of indobufen for 1 week, with a 7-day washout period between treatments. Urinary 11-dehydro-TXBj excretion averaged 58.2 ± 21.8 ng/h at baseline. TX metabolite excretion was reduced dose dependently by indobufen: by 67% at 50 mg BID, 72% at 100 mg BID, and 81% at 200 mg BID. Platelet cyclooxygenase activity, ATP release, collageninduced platelet aggregation, and bleeding time also were modified dose dependently by indobufen. Biochemical demonstration of suppressed platelet TX A2 in vivo was accompanied by evidence of inhibited platelet function as assessed ex vivo. Under pathophysiological conditions, such as NIDDM, which are associated with enhanced TX A2 synthesis, more than 95% suppression of platelet cyclooxygenase activity may be necessary to produce virtually maximal inhibition of platelet TXA2 biosynthesis in vivo.
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