Dazoxiben, a thromboxane synthetase inhibitor, in Raynaud's phenomenon

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Abstract
Dazoxiben, a specific thromboxane synthetase inhibitor, was evaluated in 21 patients with Raynaud''s phenomenon in a double-blind, placebo-controlled crossover experiment. Total fingertip blood flows were measured by plethysmography and capillary blood flows were measured by 133Xe disappearance rate. Subjects were studied in both a warm (28.degree. C) and a cold (20.degree. C) room. Arteriovenous (AV) shunt flow was estimated by subtraction of capillary flow from total flow. Ex vivo production of thromboxane B2 (TXB2) and 6-keto PGF1.alpha. was determined by specific radioimmunoassay in serum from venous blood incubated for 1 h (37.degree. C). Plasma concentrations of TXB2 and 6-keto PGF1.alpha. were also monitored. Dazoxiben (100 mg 4 times a day for 14 days) inhibited ex vivo TXB2 production (from 463.1 .+-. 69.9 to 101.8 .+-. 13.4 ng/ml per h (.hivin.X .+-. SE)); enhanced ex vivo 6-keto PGF1.alpha. production (from 1.38 .+-. 0.05 to 3.76 .+-. 0.18 ng/ml per h): and reduced plasma TXB2 concentration (from 88.1 .+-. 13.9 to 38.8 .+-. 5.9pg/ml). There were no changes in plasma concentration of 6-keto PGF1.alpha.. Dazobixen did not improve total digital blood flow, capillary flow, AV shunt flow or forearm blood flow at 28.degree. or 20.degree. C. There was no subjective improvement in frequency or severity of Raynaud''s attacks (assessed by patient diaries). Dazoxiben is evidently a potent and specific thromboxane synthetase inhibitor capable of altering arachidonic acid metabolism, but is of little or no benefit in the treatment of Raynaud''s phenomenon.