Interaction studies with bumetanide and furosemide. Effects of probenecid and of indomethacin on response to bumetanide in man

Bumetanide was administered intravenously in doses of 0.5 and 1.0 mg to eight normal subjects with and without pretreatment with probenecid or indomethacin. Probenecid did not affect either the cumulative response or the time course of response to bumetanide. This may mean that probenecid and potentially other exogenous or endogenous organic acids do not affect the renal handling of bumetanide in normal man. Indomethacin pretreatment decreased the cumulative 4-hour excretion of sodium caused by 1.0 mg bumetanide from 276 +/- 22.9 to 202 +/- 20.9 mEq (P less than 0.003). Effects on volume and chloride paralleled those of sodium, while potassium excretion was not affected. When the response was analyzed as increment in fractional excretion over basal solute excretion, determined from separate control studies, indomethacin still decreased the response, possibly indicating that endogenous prostaglandins may play a role in determining the overall response to bumetanide.
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