Effects of glipizide on water and electrolyte handling in water-loaded humans

Renal handling of H2O, Na, and K during H2O diuresis was studied in the same healthy subjects on two occasions, after the administration of either 5 mg of the sulfonylurea, glipizide, or a placebo. Following glipizide, there was no significant overall change in creatinine clearance and the calculated rate of distal Na + K delivery (CH2O + C(Na + K)) in 9 individuals. However, the clearance of free water (CH2O) and the mean fraction of Na + K reabsorbed at the diluting site increased significantly from 8.5 +/- (SEM) 0.8 to 9.8 +/- (SEM) 0.8 ml/min/100 ml GFR (p less than 0.02) and from 55 +/- (SEM) 6 to 67 +/- (SEM) 7% (p less than 0.05), respectively. The mean rate of total Na and K excretion fell following glipizide (p less than 0.05). Our results, in conjunction with the results from similar type studies, suggest that ingestion of glipizide and other sulfonylureas that lack antidiuretic properties increase CH2O, at least in part, by augmenting ion reabsorption at the diluting sites of the nephron.