Specific thromboxane synthetase inhibition and albumin excretion rate in insulin-dependent diabetes

Abstract

Albumin excretion rates (AER) were measured in 30 insulin-dependent diabetics during a 16-week double-blind, randomised, placebo-controlled study of the specific thromboxane synthetase inhibitor UK-38,485.6 of 15 subjects in the active group had microalbuminuria (defined as mean pretreatment AER 20-150 micrograms/min); in these patients AER fell from 32 +/- 3 micrograms/min to 11 +/- 1 micrograms/min at 8 weeks and 9 +/- 1 micrograms/min at 16 weeks. The AER rose again (to 29 +/- 8 micrograms/min) within 12 weeks of stopping the drug. There was no significant change in the 10 patients with microalbuminuria who received placebo. There was a strong correlation between change from baseline values and the baseline values themselves in the active, but not in the placebo group, and the change from baseline differed significantly between the two groups. There was no change in glycosylated haemoglobin or mean blood glucose levels during the study. In a separate study UK-38,485 caused significant suppression of thromboxane B2 synthesis in diabetic and non-diabetic subjects.