title: Mechanisms of the synergistic combination of metolazone and bumetanide.
abstract: 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.
mesh_terms: D000328:Adult; D001692:Biological Transport / Q000187:drug effects; D002034:Bumetanide / Q000494:pharmacology*; D002712:Chlorides / Q000378:metabolism; D004232:Diuretics / Q000494:pharmacology*; D004357:Drug Synergism; D006801:Humans; D007684:Kidney Tubules / Q000187:drug effects*; D008297:Male; D008788:Metolazone / Q000494:pharmacology*; D010710:Phosphates / Q000378:metabolism; D012964:Sodium / Q000378:metabolism; D014882:Water-Electrolyte Balance / Q000187:drug effects
chemical_list: D002712:Chlorides; D004232:Diuretics; D010710:Phosphates; D002034:Bumetanide; D012964:Sodium; D008788:Metolazone