Brater D C, Pressley R H, Anderson S A
J Pharmacol Exp Ther. 1985 Apr;233(1):70-4.
We assessed the effects of metolazone and of bumetanide alone and in combination in normal volunteers when both sodium replete and when sodium deprived. In both conditions a supra-additive natriuretic (P less than .025) and chloruretic (P less than .05) effect of the combination was observed, the magnitude of which was somewhat greater in the sodium-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 contrast, in the sodium-deprived subjects, free water clearance relative to the delivery term was diminished 72 +/- 2% with the combination compared to 64 +/- 2% for the two diuretics individually (P = .003). These data indicate that the supra-additive response is due to a synergistic effect of the combination at the diluting segment.
