The effects of amiloride (M, 20 mg/day), chlorothiazide (C, 1000 mg/day), ethacrynic acid (E, 100 MG/day) and frusemide (F, furosemide 80 mg/day, given alone and in combination, were investigated in eight patients in a 2(4) factorial study. Effects between blocks of four treatments in each sixteen-treatment replicate were confounded with higher interactions to allow for differences between early and late diuresis. 2. All patients exhibited marked diuresis, with significant mean increases in daily urinary sodium excretion (P smaller than 0.05) and urinary volume (P smaller than 0.01) induced by chlorothiazide, frusemide and ethacrynic acid (68, 69 and 38%; and 35, 40 and 34%, respectively). Amiloride appeared to be half to one-third as potent as the other diuretics. 3. Amiloride produced a significant potassium-sparing effect (P smaller than 0.01), reducing urinary potassium excretion by 30%, compared to significant urinary potassium wasting with frusemide (increase of 33%, P smaller than 0.01) and chlorothiazide (increase of 31%, P smaller than 0.05). 4. No adverse reactions occurred, but serum potassium levels twice rose to 6 mmol/l and subsided without additional therapy, and on one occasion fell to 2.5 mmol/l, requiring a potassium supplement for 4 days. 5. It was concluded from these factorial studies that amiloride is a mild diuretic and potent potassium-sparing agent acting independently and additively in combination with chlorothiazide, ethacrynic acid or frusemide. For the three latter diuretics, all two-drug interactions were simply additive also, without evidence of synergism or antagonism between drugs.
