THE ACUTE EFFECTS OF MEFRUSIDE IN MAN: A NEW DIURETIC COMPOUND

¹ Cardiovascular Research Laboratories, Department of Internal Medicine, University of Iowa, Iowa City, Iowa

Mefruside, a new diuretic compound of the 4-chloro-3-sulfonamido-benzenesulfonamide series was studied after single p.o. doses of 25 and 100 mg in human volunteers undergoing water diuresis. The drug caused natriuresis and chloruresis extending for 20 hours with only insignificant increases in potassium excretion acutely. The mean clearances of inulin and para-aminohippuric acid were lowered insignificantly only after the 100-mg dose. When hourly values were compared, a significant decrease in the mean clearance of para-aminohippuric acid was found in four of the first five hours in the 100-mg study. The clearance of free water was decreased in relation to the urine volume. Bicarbonate excretion increased, and the tubular reabsorption of phosphorus decreased. In vitro carbonic anhydrase inhibition studies revealed 50% inhibition at 7.3 x 10^-7 M concentration. No hyperglycemic effect was noted. The uric acid clearance was not decreased acutely, but elevation of serum uric acid was noted in follow-up determinations. An increase in magnesium excretion occurred whereas serum magnesium levels remained constant. Plasma renin values were depressed during these acute experiments, but with chronic administration plasma renin rose and kaluresis occurred. No objective or subjective adverse effects of mefruside were noted clinically or by studies of the hematopoietic, renal and liver function. The potency of mefruside and its effect on renal concentrating and diluting mechanisms suggest that its action is similar to that of the thiazide diuretics.