Reorientation of prostaglandin endoperoxide metabolism by a thromboxane synthetase inhibitor: in vitro and clinical observations.

1 Work with dazoxiben in vitro and in vivo suggests that a diminished capacity of platelets to synthesize thromboxane A2 results in a reorientation of the metabolism of cyclic endoperoxides. 2 Platelets of patients with congenital thromboxane synthetase deficiency show the same phenomenon. 3 In the presence of endothelium or leukocytes which have prostacyclin synthetase capacity, significant amounts of prostacyclin can be generated if thromboxane synthesis is blocked. 4 The local generation of aggregation inhibiting prostaglandins in areas of vascular damage may be an interesting therapeutic concept. 5 Pilot clinical studies of thromboxane synthetase inhibitor dazoxiben (UK 37248) in a small number of patients with peripheral arterial disease did not reveal major or consistent haemodynamic changes. 6 Attention is directed towards optimizing pharmacologically the generation and efficacy of the inhibitory prostaglandins produced when thromboxane synthetase is inhibited.