Characterization of the renal pharmacology of HP-522, a loop diuretic with uricosuric activity

Hydrochlorothiazide (HCTZ), ethacrynic acid, furosemide and HP-522 were studied in various clearance experiments in the dog. all four diuretics were more active saluretics during hydration studies. Only HP-522, ethacrynic acid and furosemide impaired TCH2O formation. Pretreatment of the animals with indomethacin, 5 mg/kg, i.v. significantly attenuated the diuretic and saluretic activity of HP-522. HP-522 was shown to lower plasma uric acid after chronic administration to chimpanzees at 10 mg/kg, p.o. for 10 days. Results from this study suggest that HP-522 appears to be a loop diuretic with at least one site of action in the medullary ascending limb of Henle's loop.