Effect of dazoxiben, a thromboxane synthetase inhibitor on skin‐blood flow following cold challenge in patients with Raynaud's phenomenon

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Abstract
The effects of dazoxiben on finger‐blood flow in response to cold challenge were studied in normal subjects and patients with Raynaud's phenomenon. In normal subjects concentrations of TXB2 and 6‐oxo‐PGF1α were measured in blood taken from dorsal hand veins following cold challenge. In a parallel multicentre study we examined the effects of dazoxiben on finger temperature and capillary blood cell velocity in patients with Raynaud's phenomenon. Dazoxiben did not affect finger arterial inflow at rest or during cold challenge in patients or controls. However in both groups, recovery was quicker after cold challenge on dazoxiben treatment. In patients median flow was 5 ml (100‐1 ml) min‐1 (range 1–10) v. 2 (0·5–15), P lt; 0·05 dazoxiben v. placebo at 15 min after cold challenge. However, in normal subjects this did not prove to be statistically significant. In normal subjects there was a fall in TXB2 concentrations and relative rise in 6‐oxo‐PGF1α following dazoxiben treatment indicating redirection of prostaglandin endoperoxides towards synthesis of PGIi. Comparison of the sum‐total output of each eicosanoid following treatment with dazoxiben revealed a 65% reduction in TXB2 concentrations (P < 0·025 compared with placebo) and a 40% increase in 6‐oxo‐PGF1α concentrations (P < 0·05 compared with placebo). However a simultaneous increase in concentrations of FPA indicated generation of thrombin, probably at the needle tip. Long‐term treatment with dazoxiben resulted in no significant change in finger‐skin temperature or capillary blood cell velocity, duration, or severity of attacks of Raynaud's phenomenon.