Drugs

, Volume 28, Issue 5, pp 426–464 | Cite as

Bumetanide

A Review of its Pharmacodynamic and Pharmacokinetic Properties and Therapeutic Use
  • A. Ward
  • R.C. Heel
Drug Evaluation

Summary

Synopsis: Bumetanide1 is a potent ‘loop’ diuretic for the treatment of oedema associated with congestive heart failure, hepatic and renal diseases, acute pulmonary congestion and premenstrual syndrome and in forced diuresis during and after surgery. Bumetanide may be given orally, intravenously or intramuscularly and produces a rapid and marked diuresis, and increased urinary excretion of sodium, chloride and other electrolytes (within 30 minutes) which persists for 3 to 6 hours. Its principal site of action is on the ascending limb of the loop of Henle, with a secondary action on the proximal tubule.

Pharmacologically, bumetanide is about 40- fold more potent thanfrusemide (furosemide), with the exception of its effects on urinary potassium excretion where its potency is lower. Studies in patients with oedema due to congestive heart failure, pulmonary oedema or hepatic disease show that oral or intravenous bumetanide 0.5 to 2 mg/day produces results comparable to those with frusemide 20 to 80 mg/day. In acute pulmonary oedema, intravenous bumetanide produces a very rapid diuresis. Higher doses of bumetanide may be required (up to 15 mg/day) in patients with chronic renal failure or nephrotic syndrome. In these patients muscle cramps are not uncommon with bumetanide, but glomerular filtration rates are unaffected. In most studies, diuretic effects were accompanied by decreased bodyweight, abdominal girth and improvements in a variety of haemodynamic parameters.

Comparison of bumetanide with frusemide at a dose ratio of 1: 40 reveals no significant differences in clinical response with the exception of renal disease, where patients with oedema appear to respond better to bumetanide.

Combination with thiazide diuretics enhances the clinical response to bumetanide. Potassium supplements and spironolactone may be beneficial additions to bumetanide where patients at risk of hypokalaemia can be identified. Clinically important side effects are infrequent, with audiological impairment occurring to a lesser extent than with frusemide. Bumetanide thus offers an important alternative to frusemide when a ‘loop’ diuretic is indicated.

Pharmacodynamic Studies: Bumetanide is a potent ‘loop’ diuretic, which produces a marked dose-related diuresis and urinary excretion of sodium and chloride in man over a dose range of 0.5 to 3.0mg. On a milligram-for-milligram basis bumetanide is 40-fold more potent than frusemide, although the dose-response curves for the two drugs are not parallel outside this dose range, and in cases such as renal impairment, where high doses may be used, a ratio of 40: 1 may be misleading. Total maximal diuresis increases by about 5- to 10-fold in healthy volunteers and patients, and urinary sodium and chloride excretion by about 10- to 20-fold, after both oral and intravenous doses of bumetanide. The fractional excretion rate of sodium is increased from less than 3% to up to 25%. The comparability of the total effects of these 2 dose routes reflects almost complete gastrointestinal absorption of oral doses. Bumetanide produces marked diuresis in states of hydropenia as well as in states of aqueous diuresis. Onset of diuresis in patients with oedematous states given oral bumetanide occurs within 30 minutes, reaches peak activity at 60 to 180 minutes and has a duration of 5 to 6 hours. Intravenous doses elicit effects within 10 minutes, and reach peak effects at 15 to 45 minutes.

The increase in total potassium excretion is about 3-fold, therefore the sodium/potassium excretion ratio is increased with bumetanide. This occurs to a greater extent with bumetanide than with frusemide or hydrochlorothiazide, thereby giving it a lesser theoretical kaliuretic potential than the latter 2 drugs. Increases in urinary calcium, magnesium and phosphate excretion also parallel those of sodium and water excretion, but may be greater than with frusemide. Urine osmolality is decreased with bumetanide. Excretion of titratable acid, bicarbonate, and ammonium ions are all increased, with negligible effects on urine pH - although renal tubular fluid may be acidified. Hyperuricaemia is commonly observed.

Bumetanide enhances renal blood flow and increases kidney volume. This precedes diuresis and is probably subject to control or mediation by local prostaglandin, kinin and kallikrein activity. Altered renal haemodynamics are probably responsible for increased plasma renin activity but are not essential for the diuretic effects of bumetanide. Glomerular filtration rate is usually unaffected, even in patients with renal insufficiency. Probenecid has been shown to inhibit the effects of bumetanide, despite raised plasma concentrations of the diuretic, but probably only after repeated or high doses. It is unlikely that bumetanide has any effect on carbonic anhydrase. Bumetanide has been shown to directly inhibit the electrolyte transport in the ascending limb of the loop of Henle. Furthermore, indirect evidence is suggestive of an additional proximal tubular site of action. Bumetanide directly inhibits the sodium-potassium-chloride cation co-transport systems in a number of cellular models and is about 60 to 100 times more potent than frusemide in such studies.

Pharmacokinetic Studies: Peak plasma concentrations of bumetanide following oral doses of 0.5 to 2mg occur after 0.5 to 2 hours and are dose related (30 to 80 Mg/L) in healthy volunteers. Absorption of bumetanide is rapid and almost complete (bioavailability up to 95%) in contrast to some commercially available frusemide formulations. A widely varying volume of distribution of 12 to 35L has been reported. Bumetanide is 93 to 95% protein bound in plasma with no appreciable binding to erythrocytes.

In man, renal elimination accounts for about half the total plasma clearance rate of 200 to 250 ml/min, the rest being cleared by hepatic metabolism or via the biliary route. Urinary recovery of 80% at 48 hours is composed primarily of unchanged drug, with unconjugated alcohols being the principal urinary metabolites. The elimination half-life of bumetanide is about 1 to 1.5 hours in healthy volunteers.

In patients with chronic hepatic or renal disease both the plasma protein-bound fraction and clearance rates may be decreased, and the half-life of bumetanide increased. There appear to be no important pharmacokinetic interactions between bumetanide and either digoxin or warfarin, or when potassium is added to or combined with bumetanide.

Therapeutic Trials: Clinical trials with bumetanide have been extensively carried out in patients with oedematous states due to congestive heart failure, liver and renal disease. However, these studies suffer from inadequate standardisation of disease severity and of the subjective and objective measurements used to gauge clinical respose to bumetanide. Overall there appears to be no significant difference between the effects of bumetanide and frusemide (in a dose ratio of 1:40), with the effects of both drugs being somewhat attenuated upon repeated doses but stabilising at above basal levels of diuresis and saliuresis. Continued efficacy for periods up to 18 months has been shown with bumetanide.

In patients with congestive heart failure, oral and intravenous bumetanide 0.5 to 2 mg/day produces a rapid increase in urinary water and electrolyte excretion, along with decreased abdominal girth, bodyweight and hepatomegaly. Where congestive heart failure is complicated by hypertension, ischaemic or valvular heart disease or non-obstructive hypertrophic cardiomyopathy, bumetanide may reduce mean arterial blood pressure, pulmonary and systemic arterial resistance, right atrial pressure, pulmonary capillary venous pressure, left ventricular end-diastolic pressure and heart rate without affecting cardiac work indexes or blood gases. At higher doses bumetanide is also effective in most congestive heart failure patients where renal insufficiency is present. In infants, a suboptimal dose of 0.015 mg/kg given as an oral solution produced both short and long term diuresis and saliuresis with no significant adverse effects.

Patients with acute pulmonary oedema or hypertension experience the necessarily rapid and intense diuresis and electrolyte excretion following intravenous and intra-arterial administration of bumetanide 1 to 3mg. However, very severely diseased patients may be resistant to clinical improvements.

Advanced liver disease of various aetiology accompanied by oedema or ascites has been successfully treated with bumetanide 1 to 4 mg/day, with the elimination of ascites and oedema, and decreases in bodyweight and abdominal girth. A successful response may be achieved in patients with both hepatic disease and renal insufficiency but, in such patients, only data on intra-arterial administration are currently available. Addition of spironolactone in patients with advanced liver disease prevents the plasma potassium decreases seen during bumetanide therapy but may not increase the diuretic response.

Bumetanide is usually an effective diuretic in patients with oedema associated with chronic renal failure and nephrotic syndrome, especially where other diuretic therapy has failed or aggravated the renal impairment. However, higher doses (up to 15 mg/day) may be necessary. In cases of severe renal insufficiency, bumetanide may not produce adequate diuresis, although natriuresis may be pronounced. Overall, comparative studies indicate an advantage in favour of bumetanide over frusemide in both short and long term use in these patients. Such high doses are more commonly associated with muscle cramps than in patients with other oedematous conditions, but glomerular filtration rate is usually unaffected and may even increase with bumetanide. However, there is some evidence to suggest that in these patients the relative potency of frusemide compared with bumetanide may be greater than the 1:40 ratio reported in other patients.

Other conditions in which bumetanide has proven useful include forced diuresis after surgery (cardiac, urological, and for Dupuytren’s contracture) and reduction of oedema in premenstrual tension, although experience in these fields is limited.

The few controlled studies where potassium was given either as a supplement to or in combination with bumetanide therapy do not indicate any advantages for potassium replacement. However, in studying this controversial area little attempt has been made to identify those patients particularly ‘at risk’ of hypokalaemia.

When bumetanide is combined with the thiazide diuretics there is a distinct supraadditive effect without affecting glomerular filtration rate. Further addition of spirono-lactone does not confer any clinical advantages, but helps allay the increased hypokalaemic effect of combined ‘loop’ and thiazide diuretic therapy.

Side Effects: The incidence of clinical side effects during treatment with bumetanide is relatively low and is approximately equivalent to that observed with frusemide (8.8% vs 7.4%, respectively). Impaired hearing and vertigo occur to a lesser extent than with frusemide (1.7% vs 3.0%) and audiometric studies have confirmed this difference between the ototoxic potential of the drugs. Muscle cramps occur in some patients treated with high doses of bumetanide, and mammary ‘abnormalities’, encephalopathy and hepatic oedema have occasionally been reported.

Abnormal laboratory results occur in 45 to 50% of patients treated with bumetanide and frusemide, but may be pre-existent in these patients and are rarely of clinical or statistical significance. Changes in serum electrolyte, creatinine and uric acid concentrations reflect the basic pharmacological activity of the drugs. Liver function test and haematological abnormalities are infrequent, although hyperglycaemia occurs in 6.6% and 10.1% of patients treated with bumetanide or frusemide, respectively. However, the possibility of a direct association between altered carbohydrate metabolism and bumetanide administration remains speculative. Despite a lesser kaliuretic effect than frusemide, bumetanide is not associated with a lower incidence of hypokalaemia.

Dosage and Administration: Bumetanide is usually administered as an oral dose of 0.5 to 2 mg/day to patients with oedematous states although this may be exceeded, especially in cases of renal oedema where doses of up to 15 mg/day may be necessary. Intravenous or intramuscular bumetanide 0.5 to 2 mg/day is usually reserved for those patients in whom oral administration is impractical, or where a very prompt onset of action is necessary, as in cases of acute pulmonary oedema.

Keywords

Renal Blood Flow Frusemide Ethacrynic Acid Postgraduate Medical Journal Potassium Excretion 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Abaza, H.H.; Hammouda, N.; El-Gohary, Y.; Abd Rabbo, H. and Aziz, Y.: Effective management of ascites of schistosomal hepatic fibrosis with the new saluretic, bumetanide. Bulletin Alexandra Faculty of Medicine 8: 193–199 (1977Google Scholar
  2. Abidi, S.E.; Miller, R.P.; Jacknowitz, A. and Quick, C.A.: Increased inner ear fluid gentamicin levels in the presence of loop diuretics. American Pharmaceutical Association, Academy of Pharmaceutical Sciences, 29th National Meeting, San Antonio, Texas, Volume 10, p. 90 (1980Google Scholar
  3. Abrahamsen, A.M.: Haemodynamics and renal function following injection of bumetanide. Acta Medica Scandinavica 201: 481–485 (1977PubMedCrossRefGoogle Scholar
  4. Abrams, J.: Intramuscular bumetanide and furosemide in congestive heart failure. Journal of Clinical Pharmacology 21: 673–679 (1981PubMedGoogle Scholar
  5. Allison, M.E.M. and Kennedy, A.C.: Diuretics in chronic renal disease. A study of high dosage frusemide. Clinical Science 41: 171 (1971Google Scholar
  6. Allison, M.E.M.; Lindsay, M.K. and Kennedy, A.C.: Oral bumetanide in chronic renal failure. Postgraduate Medical Journal 51: 47–50(1975PubMedGoogle Scholar
  7. Almeida, T.R. and Barros, P.P.: Tratamiento de la hipertension arterial con bumetanida. A Folha Medica 80: 1–4 (1980Google Scholar
  8. Andersch, B.; Hahn, L.; Wendestam, C.; Öhman, R. and Abrahamsson, L.: Treatment of premenstrual tension syndrome with bromocriptine. Acta Endocrinologica Scandinavica 88: 165–174 (1978aGoogle Scholar
  9. Andersch, B.; Hahn, L.; Andersson, M. and Isaksson, B.: Body water and weight in patients with premenstrual tension. British Journal of Obstetrics and Gynaecology 85: 546–550 (1978bPubMedGoogle Scholar
  10. Anderton, J.L. and Kincaid-Smith, P.: Diuretics: Physiological and pharmacological consideration. Drugs 1: 1–10 (1971CrossRefGoogle Scholar
  11. Aranda, J.V.; Turmen, T. and Sasyniuk, B.I.: Pharmacokinetics of diuretics and methylxanthines in the neonate. European Journal of Clinical Pharmacology 18: 55–63 (1980PubMedCrossRefGoogle Scholar
  12. Asbury, M.J.; Gatenby, P.B.B.; O’Sullivan, S. and Bourke, E.: Bumetanide: Potent new ‘loop’ diuretic. British Medical Journal 1: 211–213(1972PubMedCrossRefGoogle Scholar
  13. Aull, F.: Potassium chloride cotransport in steady-state ascites tumour cells. Does bumetanide inhibit. Biochimica et Biophysica Acta 643: 339–345 (1981CrossRefGoogle Scholar
  14. Baethke, R. and Kampf, D.: Dosis-Wirkungs-Beziehung und bumetanid bei gesunden Probanden. Arzneimittel-Forschung 25: 666–668 (1975PubMedGoogle Scholar
  15. Barclay, J.E. and Lee, H.A.: Clinical and pharmacokinetics studies on bumetanide in chronic renal failure. Postgraduate Medical Journal51 (Suppl. 6): 43–46 (1975PubMedGoogle Scholar
  16. Barrientos Guzmán, A. and Ortuño de Solo, M.T.: Diuretic evaluation of bumetanide. Medicina Clinica 73: 338–341 (1979PubMedGoogle Scholar
  17. Bennion-Pedley, J.; Donald, J.F.; Gould, C.H.G.; Lomas, D.M.; Postlethwaite, D.L. and Rivlin, R.: Patient acceptability of two diuretic/potassium supplement preparations. Journal of International Medical Research 4: 37–42 (1976PubMedGoogle Scholar
  18. Berg, K.J.; Tromsdahl, A. and Wideroe, T.E.: Diuretic action of bumetanide in advanced chronic renal insufficiency. European Journal of Clinical Pharmacology 9: 265–275 (1976PubMedCrossRefGoogle Scholar
  19. Bjorndal, N. and Lynggaard, F.: Bumetanide (Burinex) in high oral dosage in patients with chronic renal insufficiency. Uges-krift for Laeger 140: 1084–1087 (1978Google Scholar
  20. Bollerup, A.C.; Hesse, B. and Sigurd, B.: Changes of glomerular filtration rate and renal plasma flow following intravenous bumetanide in organic heart disease. Acta Pharmacologica et Toxicologica 34: 305–311 (1974PubMedCrossRefGoogle Scholar
  21. Bourke, E.: Frusemide, bumetanide and ototoxicity. Lancet 1: 917 (1976PubMedCrossRefGoogle Scholar
  22. Bourke, E.; Asbury, M.J.A.; O’Sullivan, S. and Gatenby, P.B.B.: The site of action of bumetanide in man. European Journal of Pharmacology 23: 283–289 (1973PubMedCrossRefGoogle Scholar
  23. Bourke, E.: Some aspects of the renal action and clinical pharmacology of oral bumetanide in man. Postgraduate Medical Journal 51: 23–26(1975PubMedGoogle Scholar
  24. Bourke, E.: Diuresis and serum electrolyte levels: A comparative clinical study of bumetanide (Burinex), bumetanid-KCl (Burinex K) and frusemide. Clinical Trials Journal 11:9-13 1974Google Scholar
  25. Branch, R.A.; Read, P.R.; Levine, D.; Vander Elst, E.; Shelton, J.; Rupp, W. and Ramsay, L.E.: Furosemide and bumetanide: A study of responses in normal English and German subjects. Clinical Pharmacology and Therapeutics 19: 538–545 (1976PubMedGoogle Scholar
  26. Brater, D.C. and Chennavasin, P.: Effect of probenecid on response to bumetanide in man. Journal of Clinical Pharmacology 21: 311–315 (1981PubMedGoogle Scholar
  27. Brater, D.C.; Chennavasin, P.; Day, B.; Burdette, A. and Anderson, S.: Bumetanide and furosemide. Clinical Pharmacology and Therapeutics 34: 207–213 (1983PubMedCrossRefGoogle Scholar
  28. Brater, D.C.; Kaojaren, S.; Chennavasin, P.; Burdette, A. and Anderson, S.: Comparison of pharmacokinetics of bumetanide to furosemide in subjects and patients with congestive heart failure. Pharmacologist 24: 175 (1982Google Scholar
  29. Brater, D.C.; Fox, W.R. and Chennavasin, P.: Interaction studies with bumetanide and furosemide. Effects of probenecid and of indomethacin on response to bumetanide in man. Journal of Clinical Pharmacology 21: 647–653 (1981Google Scholar
  30. Brown, R.D.: Cochlear N1 depression produced by the new ‘loop’ diuretic, bumetanide, in cats. Neuropharmacology 14: 547–553 (1975PubMedCrossRefGoogle Scholar
  31. Brown, R.D.: Comparisons of the acute effects of intravenous furosemide and bumetanide on the cochlear action potential (N,) and on the AC cochlear potential (CM) at 6KHz in cats, dogs and guinea pigs. Scandinavian Audiology (Suppl. 14): 71–83 1981aGoogle Scholar
  32. Brown, R.D.: Comparative acute cochlear toxicity of intravenous bumetanide and furosemide in the purebred Beagle. Journal of Clinical Pharmacology 21: 620–627 (1981bPubMedGoogle Scholar
  33. Brown, R.D.; Manno, J.E.; Daigneault, E.A. and Manno, B.R.: Comparative acute ototoxicity of intravenous bumetanide and furosemide in the purebred Beagle. Toxicology and Applied Pharmacology 48: 157–169(1979PubMedCrossRefGoogle Scholar
  34. Brummett, R.E.; Bendrick, T. and Hirnes, D.: Comparative ototoxicity of bumetanide and furosemide when used in combination with kanamycin. Journal of Clinical Pharmacology 21: 628–636 (1981PubMedGoogle Scholar
  35. Brunkhorst, R.; Müller-Ott, K.; Gutsche, H.V. and Niedermayer, W.: Effect of furosemide, bumetanide and piretanide on the sensor of the tuboglomerular feedback mechanism; in Robinson and Hawkins (Eds) Dialysis Transplantation Nephrology pp. 613–616 (Pitman Medical, London 1979Google Scholar
  36. Burg, M. and Green, N.: Function of the thick ascending limb of Henle’s loop. American Journal of Physiology 224: 659–668 (1973PubMedGoogle Scholar
  37. Busch, Von U.; Fedorcak, A.; Hammer, R.; Jauch, R. and Koss, F.W.: Pharmacokinetik und Metabolismus von Bumetanid bei Mensch, Hund und Ratte. Arzneimittel-Forschung 29: 315–322 (1979PubMedGoogle Scholar
  38. Candia, O.A. and Schoen, H.F.: Selective effects of bumetanide on chloride transport in bullfrog cornea. American Journal of Physiology 234: 297–301 (1978Google Scholar
  39. Capps, M.J. and Duvall, A.J.: Ototoxicity and the olivocochlear bundle. Laryngoscope 87: 1100–1108 (1977PubMedCrossRefGoogle Scholar
  40. Carriere, S.; Dandavino, R.; Rochefort, F.; Daigneault, A. and Lanoix, C.: Bumetanide, a new loop diuretic. Clinical Pharmacology and Therapeutics 20: 424–438 (1976PubMedGoogle Scholar
  41. Cohen, M.R.; Hinsch, E.; Vergona, R.; Ryan, J.; Kolis, S.J. and Schwartz, M.A.: A comparative diuretic and tissue distribution study of bumetanide and furosemide in the dog. Journal of Pharmacology and Experimental Therapeutics 197: 697–702 (1976PubMedGoogle Scholar
  42. Comis, S.D.; Leng, G. and Pratt, S.R.: The effects of frusemide, bumetanide and piretanide on the guinea pig cochlea and auditory nerve. Scandinavian Audiology (Suppl. 14): 85–93 1981Google Scholar
  43. Comis, S.D. and Pratt, S.R.: The effect of sulfamyl loop diuretics on the crossed olivo-cochlear bundle. Neuropharmacology 18: 739–741 (1979PubMedCrossRefGoogle Scholar
  44. Cortell, S.; Davidman, M.; Gennari, F.J. and Schwartz, W.B.: Catheter size as a determinant of outflow resistance and intrarenal pressure. American Journal of Physiology 223: 910–915 (1972PubMedGoogle Scholar
  45. Craven, P.A. and DeRubertis, F.R.: Calcium-dependent stimulation of renal medullary prostaglandin synthesis by furosemide. Journal of Pharmacology and Experimental Therapeutics 222: 306–314(1982PubMedGoogle Scholar
  46. Davies, D.L.; Lant, A.F.; Millard, N.R.; Smith, A.J.; Ward, J.W. and Wilson, G.M.: Renal action, therapeutic use, and pharmacokinetics of the diuretic bumetanide. Clinical Pharmacology and Therapeutics 15: 141–155 (1974PubMedGoogle Scholar
  47. De Ritis, G.; Pietropaoli, P. and Sarcinelli, L.: In dagine clinica sull’effecto diuretico della ‘bumetanide’. Acta Anaesthesiol-ogica Italica 26: 211–216(1975Google Scholar
  48. Dixon, D.W.; Barwolf-Gohlke, C. and Gunnar, R.M.: Comparative efficacy and safety of bumetanide and furosemide in long-term treatment of edema due to congestive heart failure. Journal of Clinical Pharmacology 21: 680–687 (1981PubMedGoogle Scholar
  49. Dixon, W.R.; Young, R.L.; Holazo, A.; Jack, M.L.; Weinfeld, R.E.; Alexander, K.; Liebman, A. and Kaplan, S.A.: Bumetanide: Radioimmunoassay and pharmacokinetic profile in humans. Journal of Pharmaceutical Sciences 65: 701–704 (1976PubMedCrossRefGoogle Scholar
  50. Duchin, K.L. and Hutcheon, D.E.: Comparison of bumetanide and hydrochlorothiazide on renal potassium and hydrogen ion excretion. Journal of Clinical Pharmacology 17: 453–460 (1977PubMedGoogle Scholar
  51. Duchin, K.L. and Hutcheon, D.E.: Distribution of intracortical renal blood flow induced by bumetanide in the dog. Journal of Pharmacology and Experimental Therapeutics 204: 135–140 (1978PubMedGoogle Scholar
  52. Duchin, K.L. and Hutcheon, D.E.: Effect of bumetanide on renal cortical blood flow. Journal of Clinical Pharmacology 15: 558–559 (1975Google Scholar
  53. Dunn,.G.; Kerr, I.C.; McQueen, M.J. and Thomson, R.M.: Comparison of intravenous bumetanide and frusemide during open heart surgery. Postgraduate Medical Journal 51: 72–76 (1975PubMedGoogle Scholar
  54. Ellory, J.C. and Stewart, G.W.: The human erythrocyte CL-dependent Na-K cotransport system as a possible model for studying the action of loop diuretics. British Journal of Pharmacology 75: 183–188(1982PubMedCrossRefGoogle Scholar
  55. Elmgreen, J.; Touguard, L.; Leth, A. and Christensen, M.S.: Elevated serum parathyroid hormone concentration during treatment with high ceiling diuretics. European Journal of Clinical Pharmacology 18: 363–364 (1980PubMedCrossRefGoogle Scholar
  56. Eveloff, J.; Bayerdörffer, E.; Silva, P. and Kinne, R.: Sodiumchloride transport in the thick ascending limb of Henle’s loop. Pflügers Archiv 389: 263–270 (1981PubMedCrossRefGoogle Scholar
  57. Fausti, S.A.; Frey, R.H.; Rappaport, B.Z. and Erickson, D.A.: An investigation of the effect of bumetanide on high frequency (8-20KHz) hearing in humans. Journal of Auditory Research 19: 243–250 (1979Google Scholar
  58. Feit, P.W.: Aminobenzoic acid diuretics, 2. 4-substituted-3-amino 5-sulfamylbenzoic acid derivatives. Journal of Medicinal Chemistry 14: 432–439 (1971PubMedCrossRefGoogle Scholar
  59. Feit, P.W.: Roholt, K. and Sorensen, H.: GLC determination and urinary recovery of bumetanide in healthy volunteers. Journal of Pharmaceutical Sciences 62: 375–379 (1973PubMedCrossRefGoogle Scholar
  60. Forbush, B. and Palfrey, H.C.: [3H] Bumetanide binding to membranes isolated from dog kidney outer medulla. Journal of Biological Chemistry 258: 11787–11792 (1983PubMedGoogle Scholar
  61. Frey, H.-H.: Pharmacology of bumetanide. Postgraduate Medical Journal 51: 14–18(1975PubMedGoogle Scholar
  62. Friedman, P.A. and Roch-Ramel, F.: Hemodynamic and natriuretic effects of bumetanide and furosemide in the cat. Journal of Pharmacology and Experimental Therapeutics 203: 82–91 (1977PubMedGoogle Scholar
  63. Fries, D.; Beroniade, V.; Coy, J.-L. and Delavelle, F.: Le bumétanide, nouveau diurétique actif au cours de l’insuffisance rénale chronique. Pathologie Biologie 24: 435–439 (1976PubMedGoogle Scholar
  64. Gabriel, R. and Baylor, P.: Comparison of the chronic effects of bendrofluazide, bumetanide and frusemide on plasma biochemical variables. Postgraduate Medical Journal 57: 71–74 (1981PubMedCrossRefGoogle Scholar
  65. Gatta, A.; Grassetto, M.; Merkel, G; Zuin, R.; Milani, L. and Ruol, A.: Effect of intrarenal administration of bumetanide on renal haemodynamics and function in patients with liver cirrhosis. International Journal of Clinical Pharmacology Research 1: 199–208 (1981Google Scholar
  66. Gemba, M. and Nishimura, K.: Effects of diuretics on calcium excretion and 24Ca-activated ATPase in rat kidney. Japanese Journal of Pharmacology 27: 205–211 (1977PubMedCrossRefGoogle Scholar
  67. Giugliano, D.; Varricchio, M.; Cerciello, T.; Varano, R.; Saccomanno, F. and Giannetti, G.: Bumetanide and glucose tolerance in man. Farmaco Edizione Pratica 35: 403–408 (1980PubMedGoogle Scholar
  68. Goldberg, M.; McCurdy, D.K.; Fortz, E.L. and Bluemle, L.W.: Effects of ethacrynic acid (a new saluretic agent) on renal diluting and concentrating mechanisms. Evidence for site of action in the loop of Henle. Journal of Clinical Investigation 43: 201–216(1964Google Scholar
  69. Goto, S.; Yoshitomi, H.; Miyamoto, A.; Yamada, H.; Fujii, S.; Nakayama, T. and Fujiwara, K.: Further investigations on the binding of loop diuretics to serum proteins from patients with liver disease. Journal of PharmacoBio-Dynamics 4: 865–873 (1981PubMedCrossRefGoogle Scholar
  70. Goto, S.; Yoshitomi, H.; Miyamoto, A.; Inoue, K. and Nakano, M.: Binding of several loop diuretics to serum albumin and human serum from patients with renal failure and liver disease. Journal of PharmacoBio-Dynamics 3: 667–676 (1980PubMedCrossRefGoogle Scholar
  71. Gutsche, H.-U.; Müller-Ott, K.; Brunkhorst, R. and Niedermeyer, W.: Dose-related effects of furosemide, bumetanide and piretanide on the thick ascending limb function in the rat. Canadian Journal of Physiology and Pharmacology 61: 159–165 (1983PubMedCrossRefGoogle Scholar
  72. Haas, M. and McManus, T.J.: Bumetanide inhibits (NA+K+2C1) co-transport at a chloride site. American Journal of Physiology 245: 235–240 (1983Google Scholar
  73. Hall, S.: Hyperosmolar non-ketotic diabetic syndrome precipitated by treatment with diabetics. British Medical Journal 284: 665(1982Google Scholar
  74. Halladay, S.C.; Sipes, I.G.; Carter, D.E.: Diuretic effect and metabolism of bumetanide in man. Clinical Pharmacology and Therapeutics 22: 179–187 (1977PubMedGoogle Scholar
  75. Halladay, S.C.; Carter, D.E. and Sipes, I.G.: A relationship between the metabolism of bumetanide and its diuretic activity in the rat. Drug Metabolism and Disposition 6: 45–49 (1978PubMedGoogle Scholar
  76. Halstenson, C.E. and Matzke, G.R.: Bumetanide: A new loop diuretic. Drug Intelligence and Clinical Pharmacy 17: 786–797 (1983PubMedGoogle Scholar
  77. Hayes, A.H.; Shiroff, R.A.; Limjuco, R.A. and Schneck, D.W.: Effect of bumetanide on the renal excretion of digoxin. Clinical Pharmacology and Therapeutics 25: 228 (1979Google Scholar
  78. Henning, R. and Lundvall, O.: Evaluation in man of bumetanide, a new diuretic agent. European Journal of Clinical Pharmacology 6: 224–227(1973PubMedCrossRefGoogle Scholar
  79. Herlong, H.F.; Hunter, F.M.; Koff, R.S. and Maddrey, W.C.: A comparison of bumetanide and furosemide in the treatment of ascites. Cooperative Study. Journal of Clinical Pharmacology 21: 701–705 (1981Google Scholar
  80. Hettiarachchi, J.; McInnes, G.T.; Ramsay, L.E.: Scott, P. and Shelton, J.: Bumetanide and frusemide: Qualitative differences. British Journal of Clinical Pharmacology 4: 644–645 (1977CrossRefGoogle Scholar
  81. Higashio, T.; Abe, Y. and Yamamoto, K.: Renal effects of bumetanide. Journal of Experimental Pharmacology and Therapeutics 207: 212–220(1978Google Scholar
  82. Hioki, M.; Ariga, T. and Shindo, H.: Gas Chromatographic determination of bumetanide and its urinary excretion in healthy volunteers. Annals of the Sankyo Research Laboratory 26: 85–93 (1974Google Scholar
  83. Hofstetter, A.: Bumetanide, a new diuretic. International Urology and Nephrology 6: 35–42 (1974CrossRefGoogle Scholar
  84. Holazo. A.A.; Gustafson, J.H.; Young, R.L. and Parsonnet, M.: A bioavailability study of intravenous, intramuscular and oral bumetanide. American Pharmaceutical Association, Academy of Pharmaceutical Sciences, 31st National Meeting, Orlando, Florida, Volume 11, p. 141 1981Google Scholar
  85. Holland, S.D. and Williamson, H.E.: Probenecid inhibition on bumetanide-induced natriuresis in the dog. Proceedings of the Society of Experimental Biology and Medicine 161: 299–302 (1979Google Scholar
  86. Homeida, M.; Roberts, C.J.C. and Dombey, S.L.: A single-dose comparison of piretanide and bumetanide in congestive cardiac failure. British Journal of Clinical Pharmacology 8: 173–178 (1979PubMedCrossRefGoogle Scholar
  87. Hropot, M. and Muschawek, R.: Micropuncture studies with neutral salts of so-called ‘high ceiling’ diuretics. Archives of Pharmacology 287: 56(1975Google Scholar
  88. Humair, L.: Bumétanide dans l’insuffisance rénale. Schweizerische Medizinische Wochenschrift 112: 310–314 (1982PubMedGoogle Scholar
  89. Hunter, K.R. and Underwood, P.N.: Evaluation of once-daily versus twice-daily bumetanide in heart failure. Postgraduate Medical Journal 51: 91–95 (1975PubMedGoogle Scholar
  90. Hutcheon, D.E.; Pocelinko, R. and Duchin, K.L.: Bumetanide in the treatment of hypertension; in Scriabine and Sweet (Eds) New Antihypertensive Drugs, pp. 323–336 (Spectrum Publications, New York 1976Google Scholar
  91. Hutcheon, D.; Vincent, M.E. and Sandhu, R.S.: Clinical use of diuretics in congestive heart failure. Journal of Clinical Pharmacology 21: 668–672 (1981aPubMedGoogle Scholar
  92. Hutcheon, D.E.; Vincent, M.E. and Sandhu, R.S.: Renal electrolyte excretion pattern in response to bumetanide in healthy volunteers. Journal of Clinical Pharmacology 21: 604–609 (1981bPubMedGoogle Scholar
  93. Imai, M.: Effect of bumetanide and furosemide on the thick ascending limb of Henle’s loop of rabbits and rats perfused invitro.European Journal of Pharmacology 41: 409–416 (19Google Scholar
  94. Imbs, J.L.; Schmidt, M.; Velly, J. and Schwartz, J.: Comparison of the effect of two groups of diuretics on renin secretion in the anaesthetised dog. Clinical Science and Molecular Medicine 52: 171–182 (1977PubMedGoogle Scholar
  95. Insinna, F.; Lombardo, S. and Giarusso, P.: La bumetanide nella practica clinica anche in corso di diabete. Rivista di Patologica e Clinica 36: 185–200 (1981Google Scholar
  96. Jayakumar, S. and Puschett, J.B.: Study of the sites and mechanisms of action of bumetanide in man. Journal of Pharmacology and Experimental Therapeutics 201: 251–258 (1977PubMedGoogle Scholar
  97. Jayme, D.W.: Diuretic-sensitive K+fluxes in mouse L cell fibroblasts. Federation Proceedings of the American Society of Experimental Biology 40: 1783 1981Google Scholar
  98. Jayme, D.W.; Adelberg, E.A. and Slayman, C.W.: Reduction of K+efflux in cultured mouse fibroblasts, by mutation or by diuretics, permits growth in K+-deflcient medium. Proceedings of the National Academy of Science 78: 1057–1081 (1981CrossRefGoogle Scholar
  99. Jellett, L.B.: Potassium therapy: When is it indicated? Drugs 16: 88–94(1978PubMedCrossRefGoogle Scholar
  100. Jönsson, B.; Lindstedt, E. and Söderberg, M.: Forced diuresis for flushing of the bladder after urological operation. Läkartidningen 73: 508–509 (1976PubMedGoogle Scholar
  101. Kampf, V.D. and Baethke, R.: The diuretic activity of bumetanide in a controlled comparison with furosemide in patients with various degrees of impaired renal function. Arzneimittel Forschung 30: 1015–1018(1980PubMedGoogle Scholar
  102. Karcn, F.E. and Lasagna, L.: Evaluating adverse drug reactions; in Davis (Ed.) Adverse Drug Reaction Bulletin, pp. 204–207 (Newcastle upon Tyne Regional Postgraduate Institute for Medicine and Dentistry 1976Google Scholar
  103. Karlander, S.G.; Henning, R. and Lundvall, O.: Renal effects of bumetanide, a new saluretic agent. European Journal of Clinical Pharmacology 6: 220–223 (1973PubMedCrossRefGoogle Scholar
  104. Kaufman, J.; Hamburger, R.; Matheson, J. and Flamenbaum, W.: Bumetanide-induced diuresis and natriuresis: Effect of prosta-glandin synthetase inhibition. Journal of Clinical Pharmacology 21: 663–667(1981PubMedGoogle Scholar
  105. Kaul, B.; Davidow, B. and Hutcheon, D.: Digoxin kinetics after the administration of chlorothiazide, furosemide and bumetanide. Clinical Research 25: 585A (1977Google Scholar
  106. Koene, R.A.P.: High-dosage bumetanide in patients with chronic renal failure and severe nephrotic syndrome. Netherlands Journal of Medicine 26: 262–265 (1983PubMedGoogle Scholar
  107. Koff, R.S.: The effects of a single intravenous dose of bumetanide versus furosemide in patients with ascites and edema due to alcoholic liver disease. Journal of Clinical Pharmacology 21: 706–711 (1981PubMedGoogle Scholar
  108. Kolis, S.J.; Williams, T.H. and Schwartz, M.A.: Identification of the urinary metabolites of l4C-bumetanide in the rat and their excretion by rats and dogs. Drug Metabolism and Disposition 4: 169–176 (1976PubMedGoogle Scholar
  109. Konecke, L.L.: Clinical trial of bumetanide versus furosemide in patients with congestive heart failure. Journal of Clinical Pharmacology 21: 688–690 (1981PubMedGoogle Scholar
  110. Kourouklis, C.; Christensen, O. and Aagoustakis, D.: Bumetanide in congestive heart failure. Current Medical Research and Opinion 4: 422–431 (1976PubMedCrossRefGoogle Scholar
  111. Kramer, H.J.: Effects of bumetanide on sodium transport of the isolated frog skin and on renal Na-K-ATPase. Pharmacology 14:481-489 1976Google Scholar
  112. Krause, H.H.; Dume, T.; Koch, K.M. and Ochwadt, B.: Intratubulärer Druck, glomeruläter capillardruck und Glomeru-lumfiltrat nach Furosemid und Hydrochlorothiazid. Pflügers Archiv 295: 80–89 (1967CrossRefGoogle Scholar
  113. Kubik, M.M.; Bowers, E. and Underwood, P.N.: Comparison of separate versus simultaneous administration of potassium supplement with the diuretic bumetanide. Current Medical Research and Opinion 5: 273–278 (1977PubMedCrossRefGoogle Scholar
  114. Kubik, M.M.; Bowers, E. and Underwood, P.N.: Long term experience of the routine use of bumetanide. British Journal of Clinical Practice 30: 11–14 (1976PubMedGoogle Scholar
  115. Kusakari, J.; Kambayashi, J.; Ise, I. and Kawamoto, K.: Reduction of the endocochlear potential by the new loop diuretic, bumetanide. Acta Otolaryngologica 86: 336–341 (1978Google Scholar
  116. Lant, A.: Diuretic therapy. Practitioner 219: 519–528 (1977PubMedGoogle Scholar
  117. Lant, A.F.: Methodology in clinical pharmacology: Assessment of diuretics; in Jouhar and Grayson (Eds) International Aspects of Drug Evaluation and Usage, pp. 127–142 (Churchill Livingstone, London 1973Google Scholar
  118. Lant, A.F.: Effects of bumetanide on cation and anion transport. Postgraduate Medical Journal 51 (Suppl. 6): 35–42 (1975PubMedGoogle Scholar
  119. Lau, K.; Defronzo, R.; Morrison, G.; Rascoff, J.; Goldberg, M. and Agus, Z.S.: Effectiveness of bumetanide in nephrotic syndrome: A double-blind crossover study with furosemide. Journal of Clinical Pharmacology 16: 489–497 (1976PubMedGoogle Scholar
  120. Lawson, D.H.; Boddy, K.; Gray, J.M.B.; Mahaffey, M. and Mills, E.: Potassium supplements in patients receiving long-term diuretics for oedema. Quarterly Journal of Medicine, New Series 45: 469–478 (1976Google Scholar
  121. Lemieux, G.; Beauchemin, M.; Gougoux, A. and Vinay, P.: Treatment of nephrotic oedema with bumetanide. Canadian Medical Association Transactions 125: 1111–1117 (1981Google Scholar
  122. Lubowitz, H.: The effect of bumetanide on cation transport in human red blood cells. Journal of Pharmacology and Experimental Therapeutics 203: 92–96 (1977PubMedGoogle Scholar
  123. McInnes, G.T.; Thomson, A.H.; Rapeport, W.G. and Cook, A.: Loop diuretics — infusion or bolus? Clinical Science 63: 33–34 (19Google Scholar
  124. Maack, P.; Kohl, F.-V. and Rüdiger, H.W.: Diagnostische und therapeutische einer pulmona Drucksenkung durch Bume-tanid (Fordivran®). Therapiewoche 30: 5785–5788 (1980aGoogle Scholar
  125. Maack, P.; Kohl, F.V. and Rüdiger, H.W.: Hämodynamische sofortwirkung von Bumetanid bei Patienten mit pulmonaler Hypertonie. Therapiewoche 30: 889–895 (1980bGoogle Scholar
  126. Mackie, P.H.; Thomson, M.R.; Levine, P.F. and Branch, R.A.: A comparison of the effect of frusemide and bumetanide on the diuretic response and fibrinolytic mechanisms in man. British Journal of Clinical Pharmacology 3: 613–619 (1976PubMedCrossRefGoogle Scholar
  127. Maddedu, P.; Glorioso, N.; Dessi Fulgheri, P. and Rappelli, A.: Effects on bumetanide and postura on plasma prorenin in normal subjects. Studi Sassaresi 57: 297–304 (1979Google Scholar
  128. Madsen, S. and Gronbaek, P.: Carbohydrate metabolism during short-term bumetanide therapy. Ugeskrift for Laeger 135: 2215–2217 (1973PubMedGoogle Scholar
  129. Magnussen, M.P. and Eilertsen, E.: Species differences in the diuretic activity and metabolism of bumetanide. Naunyn-Schmiedeberg’s Archives of Pharmacology 282 (Suppl.): 61 (1974Google Scholar
  130. Marcantonio, L.A.; Auld, W.H.R.; Murdoch, W.R.; Purohit, R.; Skellern, G.G. and Howes, O.A.: The pharmacokinetics and pharmacodynamics of the diuretic bumetanide in hepatic and renal disease. British Journal of Clinical Pharmacology 15: 245–252 (1983PubMedCrossRefGoogle Scholar
  131. Marcantonio, L.A.; Auld, W.H.R.; Skellern, G.G.; Howes, C.A.; Murdoch, W.R. and Purohit, R.: The pharmacokinetics and pharmacodynamics of bumetanide in normal subjects. Journal of Pharmacokinetics and Biopharmaceutics 10: 393–409 (1982PubMedGoogle Scholar
  132. Masuda, H.; Maiata, K. and Kimura, K.: The safety test of bumetanide. Annual Reports of the Sankyo Research Laboratories 25: 110–128(1973Google Scholar
  133. Mauro, G.; Cantino, G. and Vigiani, L.: Clinical evaluation of bumetanide in diuretic therapy for incompensation and cirrhosis. Clinica Terapeutica 96: 515–521 (1981PubMedGoogle Scholar
  134. McClain, R.M. and Dammers, K.D.: Toxicologic evaluation of bumetanide, a potent diuretic agent. Journal of Clinical Pharmacology 21: 543–554 (1981PubMedGoogle Scholar
  135. McGahan, M.C.; Yorio, T. and Bentley, P.J.: The mode of action of bumetanide: Inhibition of chloride transport across the amphibean cornea. Journal of Pharmacology and Experimental Therapeutics 203: 97–102 (1977PubMedGoogle Scholar
  136. McRoberts, J.A.; Erlinger, S.; Rindler, M.J. and Saier, M.H.: Furosemide-sensitive salt transport in the Madin-Darby canine kidney cell line. Journal of Biological Chemistry 257: 2260–2266 (1982PubMedGoogle Scholar
  137. Moult, P.J.A.; Lunzer, M.R.; Trash, D.B. and Sherlock, S.: Use of bumetanide in the treatment of ascites due to liver disease. Postgraduate Medical Journal 51: 81–84 (1975PubMedCrossRefGoogle Scholar
  138. Mtabaji, J.P.; Manku, M.S. and Horrobin, D.F.: Vascular actions of furosemide and bumetanide on the rat superior mesenteric vascular bed: Interactions with prolactin and prostaglandins. Canadian Journal of Physiology and Pharmacology 54: 357–366 (1976PubMedCrossRefGoogle Scholar
  139. Murchison, L.E.; Bensher, P.D. and Seymour, R.: Lack of effect of bumetanide on body potassium content in hypertension. British Journal of Clinical Pharmacology 2: 87–91 (1975PubMedGoogle Scholar
  140. Murdoch, W.R. and Auld, W.H.R.: Bumetanide - acute and long-term studies of a new high potency diuretic. Postgraduate Medical Journal 51: 10–14 (1975PubMedCrossRefGoogle Scholar
  141. Murphy, J.E.; Maneksha, S. and Brodie, N.H.: Patient preference for a combined diuretic/potassium regimen. Burinex K. Journal of International Medical Research 3: 104–107 (1975Google Scholar
  142. Nicholson, G.: Treatment of fluid retention in cirrhosis: A comparison of bumetanide and frusemide. Current Medical Research and Opinion 4: 675–679 (1977PubMedCrossRefGoogle Scholar
  143. Nielsen, C.K. and Arrigoni-Martelli, E.: Effects of rat urinary kallikrein excretion of bumetanide, bendroflumethiazide and hydralazine. Acta Pharmacologica et Toxicologica 40: 267–272 (1977PubMedCrossRefGoogle Scholar
  144. Nilsson, C.M.; Horton, E.S. and Robinson, D.S.: The effect of furosemide and bumetanide on warfarin metabolism and anticoagulant response. Journal of Clinical Pharmacology 18: 91–94(1978PubMedGoogle Scholar
  145. Nipper, H.; Kirby, S. and Iber, F.L.: The effect of bumetanide on the serum disappearance of warfarin sodium. Journal of Clinical Pharmacology 21: 654–656 (1981PubMedGoogle Scholar
  146. Odlind, B.: Relation between renal tubular secretion and effects of five loop diuretics. Journal of Pharmacology and Experimental Therapeutics 211: 238–244 (1979PubMedGoogle Scholar
  147. Odlind, B.; Beermann, B. and Lindström, B.: Coupling between renal tubular secretion and effect of bumetanide. Clinical Pharmacology and Therapeutics 34: 805–809 (1983PubMedCrossRefGoogle Scholar
  148. Ohtani, I.; Ohtsuki, K.; Omata, T.; Ouchi, J. and Saito, T.: Interaction of bumetanide and kanamycin. Journal for Otorhin-olaryngology and its Borderlands 40: 216–225 (1978Google Scholar
  149. Olesen, K.H.; Sigurd, B.; Hesse, B.; Steiness, E. and Leth, A.: Diuretic action of bumetanide in congestive heart failure. Postgraduate Medical Journal 51: 54–63 (1975Google Scholar
  150. Olesen, K.H.; Sigurd, B.; Steiners, E. and Leth, A.: Bumetanide, a new potent diuretic. Acta Medica Scandinavica 193: 119–131 (1973PubMedCrossRefGoogle Scholar
  151. Olsen, U.B. and Ahnfelt-Rønne, I.: Bumetanide induced increase of renal blood flow in conscious dogs and its relation to local hormones (PGE, kallikrein and renin). Acta Pharmacologica et Toxicologica 38: 219–228 (1976aPubMedCrossRefGoogle Scholar
  152. Olsen, U.B. and Ahnfelt-Rønne, I.: Renal cortical blood redistribution after bumetanide related to heterogenicity of cortical prostaglandin metabolism in dogs. Acta Physiologica Scandinavica 97: 369–376 (1976bPubMedCrossRefGoogle Scholar
  153. Olsen, U.B.: Observations of the early diuretic response after intravenous administration of bumetanide and furosemide in dogs. Acta Physiologica Scandinavica 93: 195–201 (1975aPubMedCrossRefGoogle Scholar
  154. Olsen, U.B.: Prostaglandin/kinin activity related to changed renal compliance after bumetanide in dogs. Acta Pharmacologica et Toxicologica 40: 430–438 (1977bPubMedGoogle Scholar
  155. Olsen, U.B.: Prostaglandin mediated natriuresis during glucagon infusion in dogs. Acta Endocrinologica 84: 429–438 (1977aPubMedGoogle Scholar
  156. Olsen, U.B.: Indomethacin inhibition of bumetanide diuresis in dogs. Acta Pharmacologica et Toxicologica 37: 65–78 (1975bPubMedCrossRefGoogle Scholar
  157. Olsen, U.B.: Clonidine-induced increase of renal prostaglandin activity and water diuresis in dogs. European Journal of Pharmacology 36: 95–101 (1976PubMedCrossRefGoogle Scholar
  158. Olsen, U.B.; Magnussen, M.P. and Eilertsen, E.: Prostaglandins, a link between renal hydro- and hemodynamic in dogs. Acta Physiologica Scandinavica 97: 369–376 (1976PubMedCrossRefGoogle Scholar
  159. Olsen, U.B.: Dissociation between renal medullary PGE2-synthesis and urine PGE2-excretion. Antagonism by bumetanide of chlorazanil induced urine PGE2-excretion in rats. Prostaglandins 21: 591–597 (1981aPubMedCrossRefGoogle Scholar
  160. Olsen, U.B.: Investigations of the role of kidney kallikrein on bumetanide induced diuresis in rats. Acta Pharmacologica et Toxicologica 49: 321–326 (1981bPubMedCrossRefGoogle Scholar
  161. Omvik, P.; Raeder, M. and Kiil, F.: Relationship between tubular driving force and urine flow. American Journal of Physiology 226: 982–988 (1974PubMedGoogle Scholar
  162. Ortiz Gonzàlez, A.O. and Mendez Martin, A.M.: Acute effects of bumetanide in healthy subjects. A comparative study with furosemide. Medicina Clinica 72: 259–264 (1979Google Scholar
  163. Ostergaard, E.H.: Magnussen, M.P.; Nielsen, C.K.; Eilertsen, E. and Frey, H.H.: Pharmacological properties of 3-n-butylamino-4-phoxy-5-sulfamylbenzoic acid (bumetanide), a new potent diuretic. Arzneimittel-Forschung 22: 66–72 (1972PubMedGoogle Scholar
  164. Palfrey, H.C.; Greengard, P. and Feit, P.W.: Specific inhibition by ‘loop’ diuretics of an anion-dependent Na+K+cotransport system in avian erythrocytes. Annals of the New York Academy of Sciences 341: 134–138 (1980aPubMedCrossRefGoogle Scholar
  165. Palfrey, H.C.; Feit, P.W. and Greengard, P.: cAMP-stimulated cation cotransport in avian erythrocytes: Inhibition by ‘loop’ diuretics. American Journal of Physiology 238: 139–148 (1980bGoogle Scholar
  166. Papazoglou, N.; Andriopoulos, J.; Prionas, D. and Tsopras, A.: Clinical observations of a new diuretic (bumetanide). Hellenic Cardiological Review 16: 288–291 (1975Google Scholar
  167. Pedrinelli, R.; Magagua, A.; Arzilli, F.; Sassano, P. and Salvetti, A.: Influence of indomethacin on the natriuretic and renin-stimulating effect of bumetanide in essential hypertension. Clinical Pharmacology and Therapeutics 6: 722–731 (1980Google Scholar
  168. Pellerito, R.; Bertola, D. and Soragna, A.: L’impiego in clinica della bumetanide. Clinica Terapeutica 98: 651–660 (1981PubMedGoogle Scholar
  169. Pentikäinen, P.J.; Penttilä, A.; Neuvonen, P.J. and Gothoni, G.: Fate of l4C-Bumetanide in man. British Journal of Clinical Pharmacology 4: 39–44 (1977PubMedCrossRefGoogle Scholar
  170. Pentikäinen, P.J.; Neuvonen, P.J.; Kekki, M. and Penttilä, A.: Pharmacokinetics of intravenously administered bumetanide in man. Journal of Pharmacokinetics and Biopharmaceutics 6: 219–228 (1980Google Scholar
  171. Pierucci, A.; Simonetti, B.M.; Stirati, G. and Cinotti, G.A.: Effects of bumetanide upon PRA and urinary kallikrein excretion in normal subjects before and after indomethacin treatment. Minerva Neurologica 27: 421–424 (1980Google Scholar
  172. Purohit, R.; Auld, W.H.R.; Marcantonio, L.A.; Murdoch, W.R. and Skellern, G.G.: The effect of hepatic and renal disease on the administration of the diuretic bumetanide. Scottish Medical Journal 27: 92 (1982Google Scholar
  173. Puschett, J.B.; Sylk, D. and Teredesai, P.P.: Uncoupling of proximal sodium bicarbonate from sodium phosphate transport by bumetanide. American Journal of Physiology 235: 403–408 (1978Google Scholar
  174. Ramsey, L.E.; McInnes, G.T.; Hittierachchi, J.; Shelton, J. and Scott, P.: Bumetanide and frusemide: A comparison of dose-response curves in healthy men. British Journal of Clinical Pharmacology 5: 243–247 (1978CrossRefGoogle Scholar
  175. Reumbert, T. and Zachariae, L.: Continued investigations into the effect of diuretics upon oedema of the hand following operation for Dupuytren’s contracture: Bumetanide Leo. Acta Orthoptica Scandinavica 44: 410–416 (1973CrossRefGoogle Scholar
  176. Rindler, M.J.; McRoberts, J.A. and Saier, M.H.: (Na+ K+-cotransport in the Madin-Darby canine kidney cell line. Journal of Biological Chemistry 257: 2254–2259 (1982PubMedGoogle Scholar
  177. Ring-Larsen, H.: Bumetanide in the treatment of hepatic ascites. Acta Medica Scandinavica 195: 411–414 (1974PubMedCrossRefGoogle Scholar
  178. Roberts, C.J.C.; Homeida, M.; Roberts, F. and Bogie, W.: Effects of piretanide, bumetanide and frusemide on electrolyte and urate excretion in normal subjects. British Journal of Clinical Pharmacology 6: 129–133(1978PubMedCrossRefGoogle Scholar
  179. Robinson, D.S.; Nilsson, C.M.; Leonard, R.F. and Horton, E.S.: Effects of loop diuretics on carbohydrate metabolism and electrolyte excretion. Journal of Clinical Pharmacology 21: 637–646 (1981PubMedGoogle Scholar
  180. Rocha, A.S. and Kokko, J.P.: Sodium chloride and water transport in the medullary thick ascending limb of Henle — Evidence for active chloride transport. Journal of Clinical Investigations 52: 612–613 (1973CrossRefGoogle Scholar
  181. Runeberg, L.; Pasternack, A.; Borgmästars, H. and von Borns-dorff, M.: Clinical trial of a new diuretic, bumetanide, in seriously ill patients. Annals of Clinical Research 6: 272–278 (1974PubMedGoogle Scholar
  182. Sández Macho, M. and Sánchez Salorio, M.: Hypotensive action of bumetanide on ocular tension. Medicina Clinica 69: 106–108 (1977Google Scholar
  183. Santi, P.A. and Duvall, A.J.: Morphological alterations of the stria vascularis after administration of the diuretic bumetanide. Acta Otolaryngologica 88: 1–12 (1979CrossRefGoogle Scholar
  184. Schönebeck, J. and Ygge, H.: Forced diuresis after transurethral prostate resection: A comparison between bumetanide and mannitol. Läkartidningen 74: 2213–2214 (1977PubMedGoogle Scholar
  185. Schwartz, M.A.: Metabolism of bumetanide. Journal of Clinical Pharmacology 21: 555–563 (1981PubMedGoogle Scholar
  186. Segal, M.B. and Pollay, M.: The secretion of cerebrospinal fluid: in Bhito et al. (Eds) The Ocular and Cerebrospinal Fluids. Proceedings of a Fogarty International Symposium. Experimental Eye Research 25 (Suppl.): 127–148 (1977Google Scholar
  187. Seth, H.C.; Coulshed, N. and Epstein, E.J.: Intravenous bumetanide in the treatment of acute and chronic pulmonary oedema. British Journal of Clinical Practice 29: 7–11 (1975PubMedGoogle Scholar
  188. Sigurd, B.; Bollerup, A.-C.; Hesse, B. and Valentin, N.: Investigations with intravenous bumetanide. Postgraduate Medical Journal 51 (Suppl. 6): 27–34 (1975PubMedGoogle Scholar
  189. Sigurd, B.; Hesse, B. and Valentin, N.: Bumetanide: A new potent diuretic. Danish Medical Bulletin 21: 63–67 (1974PubMedGoogle Scholar
  190. Sigurd, B. and Olesen, K.H.: The supra-additive natriuretic effect of addition of theophyllias ethylenediamine and bumetanide in congestive heart failure. American Heart Journal 94: 168–174 (1977PubMedCrossRefGoogle Scholar
  191. Silver, M.R.; Moller, M.B.; Owen Black, F.; Wall, C. and Puschett, J.B.: Effects of furosemide and bumetanide on auditory and vestibular function in normal human volunteers. Kidney International 23: 135 (1983Google Scholar
  192. Singh, B.B. and Watt, D.A.L.: Patient tolerance of long-term diuretic/potassium supplement therapy. Current Medical Research and Opinion 4: 117–123 (1976PubMedCrossRefGoogle Scholar
  193. Smith, D.E.: High-performance liquid Chromatographic assay for bumetanide in plasma and urine. Journal of the Pharmaceutical Sciences 71: 520–523 (1982CrossRefGoogle Scholar
  194. Smith, D.E. and Lau, H.S.H.: Determinants of bumetanide response in the dog: Effect of probenecid. Journal of Pharmacokinetics and Biopharmaceutics 11: 31–45 (1983PubMedGoogle Scholar
  195. Smith, D.E.; Lau; H.S.H. and Fox, J.L.: Application of effect-compartment model to bumetanide-indomethacin interaction in dogs. Journal of Pharmacokinetics and Biopharmaceutics 11: 355–368(1983PubMedGoogle Scholar
  196. Steward, R.; Michels, R.; Balakumaran, K.; Lubsen, J. and Hugenholtz, P.G.: Comparative diuretic and haemodynamic effects of bumetanide and Lasix in acute myocardial infarction with left ventricular failure. Abstracts of the European Congress of Cardiology, Paris, p. 187 (Jun 1980Google Scholar
  197. Stone, W.J.; Bennett, W.M. and Cutler, R.E.: Long-term bumetanide treatment of patients with edema due to renal disease. Cooperative studies. Journal of Clinical Pharmacology 21: 587–590 (1981Google Scholar
  198. Suki, W.; Rector, F.C. and Seldin, D.W.: The site of action of furosemide and other sulfonamide diuretics in the dog. Journal of Clinical Investigation 44: 1458–1469 (1965PubMedCrossRefGoogle Scholar
  199. Tuzel, I.H.: Comparison of adverse reactions to bumetanide and furosemide. Journal of Clinical Pharmacology 21: 615–619 (1981PubMedGoogle Scholar
  200. Ueberschär, S. and Bakker-Grunwald, T.: Bumetanide-sensitive potassium transport and volume regulation in turkey eryth-rocytes. Biochimica et Biophysica Acta 731: 243–250 (1983PubMedCrossRefGoogle Scholar
  201. Urakabe, S.; Shirai, D.; Yuasa, S.; Kimura, G.; Orita, Y. and Abe, H.: Comparative study of the effects of different diuretics on the permeability properties of the toad bladder. Comparative Biochemistry and Physiology 53: 115–119 (1976CrossRefGoogle Scholar
  202. Valderrabano Quintana, F.; Jofre Ibanez, R.; Resano Valls, M.; Anaya Lomana, F.; Lopez Gomez, J.M. and Alles Gamberale, A.: Efecto diurético de la bumetanida en la insufficiencia renal crónica. Revista Clinica Espanola 148: 423–428 (1978PubMedGoogle Scholar
  203. Velasquez, M.T.; Wan, S.H.; Barr, J.W. and Maronde, R.F.: Effect of probenecid on the natriuresis and renin release induced by bumetanide in man. Journal of Clinical Pharmacology 21: 657–662 (1981PubMedGoogle Scholar
  204. Velasquez, M.T.; Wan, S.H. and Maronde, R.F.: Bumetanide-induced rise in plasma renin activity. Clinical Pharmacology and Therpeutics 24: 186–191 (1978Google Scholar
  205. Vincent, M.E. and Hutcheon, D.E.: Studies on the sites of renal hydrogen ion secretion in response to bumetanide in the dog. Federation Proceedings 40: 648 (1981Google Scholar
  206. Vogh, B.P. and Langham, M.R.: The effect of furosemide and bumetanide on cerebrospinal fluid formation. Brain Research 221: 171–183 (1981PubMedCrossRefGoogle Scholar
  207. Ward, O.C. and Lam, L.K.T.: Bumetanide in heart failure in infancy. Archives of Disease in Childhood 52: 877–882 (1977PubMedCrossRefGoogle Scholar
  208. Wen, S.F.: Micropuncture studies of phosphate transport in the proximal tubule of the dog. Journal of Clinical Investigations 53: 143–153 (1974CrossRefGoogle Scholar
  209. Whelton, A.: Long-term bumetanide treatment of renal edema. Comparison with furosemide. Journal of Clinical Pharmacology 21: 591–598 (1981Google Scholar
  210. White, M.G.: The effect of intravenous bumetanide in man with normal and low renal function. Journal of Clinical Pharmacology 21: 581–586 (1981PubMedGoogle Scholar
  211. White, M.G.; van Gelder, J. and Eastes, G.: The effect of loop diuretics on the excretion of Na+ Ca2+and Cl~). Journal of Clinical Pharmacology 21: 610–614 (1981PubMedGoogle Scholar
  212. Whiting, P.H.; Petersen, J. and Simpson, J.G.: Gentamicin-induced nephrotoxicity in mice: Protection by loop diuretics. British Journal of Experimental Pathology 62: 200–205 (1981PubMedGoogle Scholar
  213. Wynn, V.; Harper, P. and Freire, A.: Bioavailability of potassium from Burinex K. Journal of International Medical Research 2: 314–316 (1974Google Scholar
  214. Ziacchi, V.; Rossi, A. and Lomanto, B.: Haemodynamic modifications induced by intravenous bumetanide in congestive heart failure. Giornale Italiano di Cardiologia 11: 104–109 (1981PubMedGoogle Scholar

Copyright information

© ADIS Press Limited 1984

Authors and Affiliations

  • A. Ward
    • 1
  • R.C. Heel
    • 1
  1. 1.ADIS Drug Information ServicesBirkenhead, Auckland 10New Zealand

Personalised recommendations