Effect of long-term administration of picotamide on baseline and exercise-induced urinary albumin excretion in patients with type II diabetes mellitus and incipient nephropathy.

The present pilot study investigated the effect of long-term treatment with picotamide on baseline and exercise-induced urinary albumin excretion levels in normotensive patients with type II diabetes mellitus. Six patients with type II diabetes were studied: four patients (two men and two women; mean age, 52 +/- 11 years) were treated for 9 months with picotamide (300 mg, TID) and two patients who did not receive the study medication served as controls. Three of the picotamide-treated patients were given a cycloergometric exercise test at baseline and after 3 and 6 months of therapy to evaluate the effects of the drug on exercise-induced microalbuminuria. Microalbuminuria at rest was measured in all patients at baseline and after 3, 6, and 9 months. At the end of the study, all the picotamide-treated patients demonstrated a significant decrease in microalbuminuria at rest (from 41.7 +/- 12.7 micrograms/min at baseline to 11.8 +/- 3 micrograms/min after 9 months) and after exercise (peak at baseline 103 +/- 36 micrograms/min vs 65.8 +/- 11 micrograms/min after 6 months). Conversely, in the two controls, microalbuminuria at rest increased from 45.1 +/- 0.9 micrograms/min at baseline to 151 +/- 59 micrograms/min at the end of the 9-month study period. (All values given as mean +/- SEM.) In conclusion, long-term administration of picotamide was effective in reducing abnormal exercise-induced microalbuminuria and albuminuria at rest. These findings suggest that long-term treatment with picotamide of normotensive patients with type II diabetes mellitus and incipient nephropathy may slow the progression of the nephropathy in its early stages.

Picotamide, a dual TXB synthetase inhibitor and TXB receptor antagonist, reduces exercise-induced albuminuria in microalbuminuric patients with NIDDM.

We investigated the short-term effect of the TXB inhibitor picotamide on albuminuria induced by exercise in 15 microalbuminuric (i.e., with UAE at rest between 20 and 200 micrograms/min) type II diabetic patients (12 men and 3 women, age 56 +/- 2, BMI 28 +/- 1 kg/m2) and in six normal age-matched control subjects. The diabetic subjects performed five submaximal exercise tests (90% of theoretical heart rate) on a cycle ergometer: the first two under basal conditions; the third and fifth after subjects had received picotamide (900 mg/day) or placebo (3 tablets/day) for 10 days; the fourth exercise always was performed after 10 days of wash-out. Control subjects performed two exercises: the first in baseline conditions and the second after 10 days of picotamide administration (900 mg/day). When diabetic patients were untreated, a significant (P < 0.05) increase in UAE with respect to baseline levels was observed immediately after and 1 h after the exercise test. After picotamide administration, UAE significantly decreased (P < 0.05) immediately after and 1 h after exercise, as compared with diabetic patients given a placebo. In normal subjects, exercise was followed by a slight increase in UAE, which was not significantly affected by picotamide administration. Our results show that short-term administration of picotamide is associated with a reduction in UAE after exercise in type II diabetes patients with microalbuminuria while at rest. Picotamide, a TXB synthetase and receptor inhibitor, may decrease exercise-induced albuminuria in diabetic patients through a reduction in circulating TXB levels and inhibition of TXB action, which in turn may act by lowering glomerular capillary hydraulic pressure.