Pharmacology, Therapeutic Efficacy, and Adverse Effects of Bumetanide, A New “Loop” Diuretic

Abstract

Bumetanide is a recently developed natriuretic and diuretic agent, belonging to the "loop" class of diuretics. Since it is rapidly and almost completely absorbed after oral administration, oral and parenteral formulations have a similar pharmacokinetic profile. Peak plasma levels are achieved approximately 30 min after oral administration. The apparent half-life is 1.2-1.5 hr, and the volume of distribution is about 25 liters. Plasma clearance is 228-255 ml/min. Bumetanide is promptly and almost completely eliminated by metabolism of the butyl side chain and urinary excretion of the parent drug and its metabolites. The principle renal site of action is the ascending limb of the loop of Henle, with a minor effect on the proximal tubule. The drug causes decreases in both free water clearance (during water diuresis) and solute free water reabsorption (during hydropenia), increased fractional delivery of sodium chloride to the distal tubule and a natriuresis approaching 20% of the filtered load of sodium, calciuria, phosphaturia, and minimal bicarbonaturia. Extensive clinical studies have been conducted with both oral and parenteral bumetanide in patients with a variety of edematous conditions. The agent has been clearly demonstrated to be an effective diuretic in the treatment of edema due to cardiac disease (congestive heart failure) and edema, with or without ascites, due to hepatic disease. Bumetanide has also been shown effective in treating edema due to renal disease, even when modest to severe renal insufficiency is present, and it may be useful in the treatment of edema refractory to other loop diuretics. As would be predicted for any potent diuretic, bumetanide administration has been associated with hypokalemia, hypochloremia, metabolic aklalosis, hyperuricemia, and prerenal azotemia. Alterations in glucose metabolism are an inconsistent finding. Transient thrombocytopenia and granulocytopenia have been noted, but no consistent or important alterations in biochemical parameters have been observed. In some patients, especially those with renal failure receiving high doses, myalgias and muscle tenderness have been described. To date only a very limited potential for ototoxicity has been observed. Bumetanide has been administered without difficulty to patients having side effects from other loop diuretics.

Effects of bumetanide on neurobehavioral function in children and adolescents with autism spectrum disorders

“…1, 2, 3, 4, 5, 6, 7, 8, 9, 12, 13, 14 Used since 1975 in adults and since 1986 in children to treat hypertension, bronchopulmonary dysplasia, nephritic syndromes and congestive heart failure, bumetanide has limited side effects restricted primarily to hypokalemia. 15, 16 Bumetanide is therefore a good candidate to test clinically.…”

Differences in the Duration of Diuretic Effects and Impact on the Renin-Angiotensin-Aldosterone System of Furosemide in Healthy Dogs

“…The adverse effects of loop diuretics include natriuresis, kaliuresis and hypovolemia; these drugs may also induce dehydration, hypokalemia and azotemia [3,12]. In humans, chronic infusion of furosemide reduces the risk of adverse effects such as hypotension and ototoxicity due to lower peak serum concentrations [18].…”

Disruption of Ion Homeostasis in the Neurogliovascular Unit Underlies the Pathogenesis of Ischemic Cerebral Edema

“…Post-ischemic treatment with bumetanide reduces glutamate-triggered Na + and Cl − accumulation in neurogliovascular cells by more than 50 % [27, 32]. Bumetanide is safe [35] and produces relatively few side effects in humans [36]. Its inhibition of NKCC1 to modulate intracellular Cl − concentrations is currently being explored as therapy for neonatal seizures, temporal lobe epilepsy, and other disorders in which abnormal Cl − gradients are suspected to play a role [37], and two clinical trials are underway (ClinicalTrials.gov identifiers NCT00830531 and NCT01434225).…”