Combined effect of bumetanide and metolazone in normal volunteers

Bumetanide 1 to 2 mg or metolazone 2.5 mg were administered by mouth separately and then in combination to eight normal men and women in order to determine whether a sequential blockade of sodium reabsorption with diuretic agents that act at different sites within the nephron leads to a supra-additive diuretic effect. All three treatment regimens resulted in a significant weight loss and increased urine volume and the excretion of sodium, potassium, and chloride. A prolonged diuretic effect lasting up to 48 hours after administration occurred with metolazone alone. Although absolute and fractional chloride and potassium excretion and urine volume were higher after combined therapy (P less than .05 or better) than after either drug alone, absolute sodium excretion after combination therapy was higher than excretion after bumetanide (P less than .05) but not after metolazone. The percent of fractional sodium excretion after both drugs was greater than after either drug alone (P less than .05). However, excretion of chloride, sodium, potassium, and fluid on the combined therapy day was less than the sum of excretion on each single drug therapy day. Thus, the combination of bumetanide and metolazone did not have a supra-additive effect in normal subjects.