MECHANISMS OF THE SYNERGISTIC COMBINATION OF METOLAZONE AND BUMETANIDE

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Abstract
The effects of metolazone and bumetanide [diuretic drug] alone and in combination were assessed in normal volunteers when both Na was replete and when Na was deprived. In both conditions a supra-additive natriuretic (P < 0.025) and chloruretic (P < 0.05) effect of the combination was observed, the magnitude of which was somewhat greater in the Na-deprived state. Neither phosphate excretion nor an index of delivery to the diluting segment was supra-additive, indicating that the synergistic effect most likely did not emanate from the proximal tubule. In the Na-deprived subjects, free water clearance relative to the delivery term was diminished 72 .+-. 2% with the combination compared to 64 .+-. 2% for the 2 diuretics individually (P = 0.003). The supra-additive response is due to a synergistic effect of the combination at the diluting segment.