title: Study of the sites and mechanisms of action of bumetanide in man.
abstract: Acute clearance studies were performed in normal subjects to establish the site(s) and mechanism of action of the new diuretic agent, bumetanide (3-n-butylamino-4-phenoxy-5-sulfamylbenzoic acid), in the human kidney. When the drug was administered during water diuresis, solute-free water formation was unchanged associated with a peak increment in fractional sodium excretion of approximately 15% of filtered load. However, studies performed in hydropenic subjects demonstrated a virtual abolition of free water reabsorption. The diuretic caused a mild phosphaturia which did not appear to be related to alterations in parathyroid hormone. Furthermore, whereas net hydrogen ion excretion and urinary pH were unchanged, the excretion of ammonium ion, titratable acidity and bicarbonate all increased mildly. Taken together, the data suggest that the primary site of action of bumetanide is the medullary portion of the ascending limb of the loop of Henle, but that in addition, bumetanide inhibits the transport of sodium in the proximal nephron. Despite the fact that the drug is a sulfonamide derivative, its proximal activity seems unrelated to a carbonic anhydrase inhibitory effect. More likely the agent interferes with proximal reabsorption by impairing sodium-phosphate linked transport.
mesh_terms: D000284:Administration, Oral; D002034:Bumetanide / Q000008:administration & dosage / Q000494:pharmacology*; D004231:Diuresis / Q000187:drug effects; D004232:Diuretics / Q000494:pharmacology*; D004573:Electrolytes / Q000652:urine; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D007263:Infusions, Parenteral; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D008297:Male; D014883:Water-Electrolyte Imbalance / Q000378:metabolism
chemical_list: D004232:Diuretics; D004573:Electrolytes; D002034:Bumetanide