Clinical Investigation

Kidney International (1984) 26, 183–189; doi:10.1038/ki.1984.153

Bumetanide and furosemide in heart failure

D Craig Brater1, Bart Day1, Ann Burdette1 and Shirley Anderson1

1Departments of Pharmacology and Internal Medicine, The University of Texas Health Science Center at Dallas, Dallas, Texas

Correspondence: Dr D C Brater, Departments of Pharmacology and Internal Medicine, The University of Texas Health Science Center at Dallas, 5323 Harry Hines Boulevard, Dallas, Texas 75235, USA

Received 8 March 1983; Revised 30 January 1984.

Top

Abstract

Bumetanide and furosemide in heart failure. We assessed the handling of and response to oral bumetanide (1.0 and 2.0 mg) and to furosemide (40 and 80 mg) in 20 patients with stable, compensated congestive heart failure (CHF), comparing the two drugs and, in addition, examining differences from normal subjects. Bumetanide and furosemide were similar in time course of absorption, but patients with CHF had considerably prolonged absorption compared to normal subjects causing attainment of lower peak concentrations of drug. In both CHF and normal subjects, more bumetanide than furosemide was absorbed. The elimination half-life of furosemide was approximately twice that of bumetanide, and both were about two times longer than respective values in normal subjects. "Dose"-response curves were shifted downward from normal with both drugs. In patients with CHF, overall response did not differ between bumetanide and furosemide. The two drugs exhibit subtle differences, the clinical importance of which appears to be negligible from this study. Importantly, however, both drugs showed delayed absorption causing attainment of peak urinary excretion rates of diuretic two- to threefold lower than in normal subjects. This effect along with the abnormal responsivity of the tubule may contribute to the "resistance" to oral doses of diuretics observed clinically even though no quantitative malabsorption of drug occurs.

Le bumétanide et le furosémide dans l'insuffisance cardiaque. Nous avons mesuré l'élimination et la réponse au bumétanide (1,0 et 2,0 mg) et au furosémide (40 et 80 mg) oraux chez 20 malades atteints d'une insuffisance cardiaque congestive (CHF) stable, compensée, en comparant les deux médicaments, et, en outre, en examinant les différences par rapport aux sujets normaux. Le bumétanide et le furosémide étaient identiques en ce qui concerne la durée d'absorption, mais les malades atteints de CHF avaient une absorption considérablement prolongée par rapport aux normaux, ce qui permettait d'atteindre des concentrations maximales de médicament plus faibles. Chez les CHF comme chez les sujets normaux, plus de bumétanide était absorbé que de furosémide. La demi-vie d'élimination du furosémide était environ le double de celle du bumétanide, et pour chacun était environ deux fois plus grande que leur valeur respective chez les sujets normaux. Les courbes "dose" réponse étaient décalées vers le bas par rapport à la normale avec les deux médicaments. Chez les malades atteints de CHF, la réponse globale ne différait pas entre le bumétanide et le furosémide. Ces deux médicaments présentent des différences minimes dont l'importance clinique parait négligeable au vu de cette étude. Cependant il est important de noter que les deux médicaments ont présenté une absorption retardée entrainant des vitesses d'excrétion urinaires maximales des diurétiques 2 à 3 fois moindres que chez les sujets normaux. Cet effet, associé à une réponse tubulaire anormale, pourrait contribuer à la "résistance" aux doses orales de diurétiques observées en clinique, même lorsqu'il n'y a pas de malabsorption médicamenteuse quantifiable.

Top

References

  1. Flamenbaum W, Friedman R: Pharmacology, therapeutic efficacy, and adverse effects of bumetanide, a new "loop" diuretic. Pharmacotherapy 2:213–222, 1982
  2. Ramsay LE, McInnes GT, Hettiarachi J, Shelton J, Scott P: Bumetanide and frusemide: A comparison of dose-response curves in healthy men. Br J Clin Pharmacol 5:243–247, 1978 | PubMed | ChemPort |
  3. Brater DC: Resistance to diuretics: Emphasis on a pharmacological perspective. Drugs 22:477–494, 1981 | PubMed | ChemPort |
  4. Dixon WR, Young RL, Holazo A, Jack ML, Weinfeld RE, Alexander K, Liebman A, Kaplan SA: Bumetanide: Radioimmunoassay and pharmacokinetic profile in humans. J Pharm Sci 65:701–704, 1976
  5. Marcantonio LA, Auld WHR: Determination of the diuretic bumetanide in biological fluids by high-performance liquid chromatography. J Chromatogr 183:118–123, 1980
  6. Brater DC, Seiwell R, Anderson S, Burdette A, Dehmer GJ, Chennavasin P: Absorption and disposition of furosemide in congestive heart failure. Kidney Int 22:171–176, 1982
  7. Chennavasin P, Seiwell R, Brater DC, Liang WMM: Pharmacodynamic analysis of the furosemide-probenecid interaction in man. Kidney Int 16:187–195, 1979 | PubMed | ChemPort |
  8. Chennavasin P, Seiwell R, Brater DC: Pharmacokinetic-dynamic analysis of the indomethacin-furosemide interaction in man. J Pharmacol Exp Ther 215:77–81, 1980
  9. Smith DE, Lin ET, Benet LZ: Absorption and disposition of furosemide in healthy volunteers, measured with a metabolite-specific assay. Drug Metab Dispos 8:337–342, 1980
  10. Gibaldi M, Perrier D: Pharmacokinetics. New York, Marcel Dekker, Inc., 1975
  11. Sedman AJ, Wagner JG: CSTRIP, a fortran IV computer program for obtaining initial polyexponential parameter estimates. J Pharm Sci 65:1006–1010, 1976 | Article | PubMed | ChemPort |
  12. Metzler CM, Elfring GL, McEwan AJ: A package of computer programs for pharmacokinetic modeling (abstract). Biometrics 30:562, 1974
  13. Boxenbaum HG, Riegelman S, Elashoff RM: Statistical estimations in pharmacokinetics. J Pharmacokinet Biopharm 2:123–148, 1974 | Article | PubMed | ChemPort |
  14. Brater DC, Chennavasin P, Day B, Burdette A, Anderson S: Bumetanide and furosemide. Clin Pharmacol Ther 34:207–213, 1983 | PubMed | ChemPort |
  15. Odlind B: Relation between renal tubular secretion and effects of five loop diuretics. J Pharmacol Exp Ther 211:238–244, 1979
  16. Kaojarern S, Day B, Brater DC: The time course of delivery of furosemide into urine is an independent determinant of overall response. Kidney Int 22:69–74, 1982 | PubMed | ChemPort |
  17. Davies DL, Lant AF, Millard NR, Smith AJ, Ward JW, Wilson GM: Renal action, therapeutic use, and pharmacokinetics of the diuretic bumetanide. Clin Pharmacol Ther 15:141–155, 1974
  18. Pentikainin PJ, Penttila A, Neuvonen PJ, Gothoni G: Fate of [14C]-bumetanide in man. Br J Clin Pharmacol 4:39–44, 1977
  19. Pentikainen PJ, Nuevonen PJ, Kekki M, Penttila A: Pharmacokinetics of intravenously administered bumetanide in man. J Pharmacokinet Biopharm 8:219–228, 1980
  20. Cutler RE, Blair AD: Clinical pharmacokinetics of furosemide. Clin Pharmacokinet 4:279–296, 1979
  21. Benet LZ: Pharmacokinetics/pharmacodynamics of furosemide in man: A review. J Pharmacokinet Biopharm 7:1–27, 1979
  22. Rose HJ, O'Malley K, Pruitt AW: Depression of renal clearance of furosemide in man by azotemia. Clin Pharmacol Ther 1:141–146, 1976
  23. Andreasen F, Hansen HE, Mikkelsen E: Pharmacokinetics of furosemide in anephric patients and in normal subjects. Eur J Clin Pharmacol 13:41–48, 1978
  24. Beermann B, Dalen E, Lindstrom B: Elimination of furosemide in healthy subjects and in those with renal failure. Clin Pharmacol Ther 2:70–78, 1977
  25. Cutler RE, Forrey AW, Christopher TG, Kimpel BM: Pharmacokinetics of furosemide in normal subjects and functionally anephric patients. Clin Pharmacol Ther 15:588–596, 1974
  26. Rane A, Villeneuve JP, Stone WJ, Nies AS, Wilkinson GR, Branch RA: Plasma binding and disposition of furosemide in the nephrotic syndrome and in uremia. Clin Pharmacol Ther 24:199–207, 1978
  27. Tilstone WJ, Fine A: Furosemide kinetics in renal failure. Clin Pharmacol Ther 23:644–650, 1978 | PubMed | ISI | ChemPort |
  28. Brater DC, Chennavasin P, Seiwell R: Furosemide in patients with heart failure. Shift of the dose-response relationship. Clin Pharmacol Ther 28:182–186, 1980 | PubMed | ChemPort |
  29. Benet LZ, Greither A, Meister W: Gastrointestinal absorption of drugs in patients with cardiac failure, in The Effect of Disease States on Pharmacokinetics of Drugs, edited by Benet LZ, Washington, D.C., American Pharmaceutical Association, 1976, pp 33–50
  30. Brater DC: Pharmacodynamic considerations in the use of diuretics. Annu Rev Pharmacol Toxicol 23:45–62, 1983 | Article | PubMed | ChemPort |

Extra navigation

.
ADVERTISEMENT