Skip to main content
Log in

Pharmacokinetics/pharmacodynamics of furosemide in man: A review

  • Published:
Journal of Pharmacokinetics and Biopharmaceutics Aims and scope Submit manuscript

Abstract

The pharmacokinetics of furosemide and the attempt to correlate biological fluid measurements with diuretic response have been the subject of a large number of studies since the original reports of HajdÚ, Rupp, and coworkers in the mid-1960s. This article attempts to critically review these studies under seven different sections: furosemide pharmacokinetics in normal volunteers, furosemide pharmacokinetics in patients with decreased renal function, furosemide pharmacokinetics in patients with congestive heart failure, furosemide metabolism and assay methods, furosemide bioavailability, dose-response relationships, and the role of inhibitors and mediators on furosemide effects. The literature is reviewed through August 1978.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. K. E. Kim, G. Onesti, J. H. Moyer, and C. Swartz. Ethacrynic acid and furosemide: Diuretic and hemodynamic effects and clinical uses.Am. J. Cardiol. 27:407–415 (1971).

    Article  CAS  PubMed  Google Scholar 

  2. W. M. Kirkendall and J. M. Stein. Clinical pharmacology of furosemide and ethacrynic acid.Am. J. Cardiol. 22:162–167 (1968).

    Article  CAS  PubMed  Google Scholar 

  3. H. R. Jacobson and J. P. Kokko. Diuretics: Sites and mechanisms of action.Ann. Rev. Pharmacol. Toxicol. 16:201–204 (1976).

    Article  CAS  Google Scholar 

  4. M. B. Burg. Tubular chloride transport and the mode of action of some diuretics.Kidney Int. 9:189–197 (1976).

    Article  CAS  PubMed  Google Scholar 

  5. J. F. Seely and J. H. Dirks. Site of action of diuretic drugs.Kidney. Int. 11:1–8 (1977).

    Article  CAS  PubMed  Google Scholar 

  6. M. B. Burg, L. Stoner, J. Cardinal, and N. Green. Furosemide effect on isolated perfused tubules.Am. J. Physiol. 225:119–124 (1973).

    CAS  PubMed  Google Scholar 

  7. P. Deetjen. Mikropunktionsuntersuchungen zur Wirkung von Furosemide.Pflügers Arch. 284:184–190 (1965).

    Article  CAS  Google Scholar 

  8. J. B. Hook and H. E. Williamson. Influence of probenecid and alterations in acid-base balance of the saluretic activity of furosemide.J. Pharmacol. Exp. Ther. 149:404–408 (1965).

    CAS  PubMed  Google Scholar 

  9. A. C. Barger and J. A. Herd. Study of renal circulation in the unanesthetized dog with inert gases. I. External counting.Proc. III Int. Congr. Nephrol. 1:95 (1966).

    Google Scholar 

  10. A. G. Birtch, R. M. Zakheim, L. G. Jones, and A. C. Barger. Redistribution of renal blood flow produced by furosemide and ethacrynic acid.Circ. Res. 21:869–878 (1967).

    Article  CAS  PubMed  Google Scholar 

  11. J. C. McGiff, K. Crowshaw, and H. D. Itskovitz. Prostaglandins and renal function.Fed. Proc. 33:39–47 (1974).

    CAS  PubMed  Google Scholar 

  12. L. M. Slotkoff. Prostaglandin A, in hypertensive crisis.Ann. Intern. Med. 81:345–347 (1974).

    Article  CAS  PubMed  Google Scholar 

  13. G. R. Zins. Renal prostaglandin.Am. J. Med. 58:14–24 (1975).

    Article  CAS  PubMed  Google Scholar 

  14. K. Abe, Y. Otsuka, T. Saito, S. Miyazak, M. Yasujima, N. Irokawa, M. Seino, S. Ciba, and K. Yoshinaga. Renal effects of prostaglandin E1 in hyprertensive patients.J. Exp. Med. 116:351–358 (1975).

    CAS  Google Scholar 

  15. J. B. Lee, R. V. Patak, and B. K. Mookerjee. Renal prostaglandins and the regulation of blood pressure and sodium and water homeostasis.Am. J. Med. 60:798–816 (1976).

    Article  CAS  PubMed  Google Scholar 

  16. K. J. Stone and M. Hart. Inhibition of renal PGE2-9-ketoreductase by diuretics.Prostaglandins 12:197–207 (1976).

    Article  CAS  PubMed  Google Scholar 

  17. J. R. Paulsrud and O. N. Miller. Inhibition of 15-OH prostaglandin dehydrogenase by several diuretic drugs.Fed. Proc. 33:590 (1974).

    Google Scholar 

  18. M. A. Kirschenbaum, N. White, J. H. Stein, and T. A. Ferris. Redistribution of renal cortical blood flow during inhibition of prostaglandin synthesis.Am. J. Physiol. 227:801 (1974).

    CAS  PubMed  Google Scholar 

  19. R. V. Patak, B. K. Mookerjee, C. J. Bentzel, P. E. Hysert, M. Babet, and J. B. Lee. Antagonism of the effects of furosemide by indomethacin in normal and hypertensive man.Prostaglandins 10:649–659 (1975).

    Article  CAS  PubMed  Google Scholar 

  20. E. Oliw, G. Köver, C. Larsson, and E. Änggard. Reduction by indomethacin of furosemide effects in the rabbit.Eur. J. Pharmacol. 38:95–100 (1976).

    Article  CAS  PubMed  Google Scholar 

  21. M. D. Bailie, K. Crosslan, and J. B. Hook. Natriuretic effect of furosemide after inhibition of prostaglandin synthetase.J. Pharmacol. Exp. Ther. 199:469–476 (1976).

    CAS  PubMed  Google Scholar 

  22. B. Calesnick, J. A. Christensen, and M. Richter. Absorption and excretion of furosemide-S35 in human subjects.Proc. Soc. Exp. Biol. Med. 123:17–22 (1966).

    Article  CAS  PubMed  Google Scholar 

  23. J. Gayer. Die renale Exkretion des neuen diureticum Furosemid.Klin. Wochenschr. 43:898–902 (1965).

    Article  CAS  PubMed  Google Scholar 

  24. W. Rupp and P. HajdÚ. Pharmacokinetics and pharmacodynamics of a diuretic agent. In H. J. Dengler (ed.),Symposium on Pharmacological and Clinical Significance of Pharmacokinetics, F. K. Schattauer Verlag, Stuttgart, 1970, pp. 105–111.

    Google Scholar 

  25. A. Haussler and P. HajdÚ. Untersuchungen mit dem salidiureticum 4-Chlor-N-(2-furylmethyl)-5-sulfamyl-anthranilsÄure.Arzneimittel-Forsch. 14:710–713 (1964).

    Google Scholar 

  26. L. Z. Benet. Choice of appropriate predicting models in multiple-dose chemotherapy. InCurrent Chemotherapy, Vol. I, W. Siegenthaler and R. Lüthy (eds.),Proceedings of the 10th International Congress of Chemotherapy, Zurich, Switzerland, September 1977, American Society for Microbiology, Washington, D.C., 1978, pp. 29–30.

    Google Scholar 

  27. R. E. Cutler, A. W. Forrey, T. G. Christopher, and B. M. Kimpel. Pharmacokinetics of furosemide in normal subjects and functionally anephric patients.Clin. Pharmacol. Ther. 15:588–596 (1974).

    CAS  PubMed  Google Scholar 

  28. M. R. Kelly, R. E. Cutler, A. W. Forrey, and B. M. Kimpel. Pharmacokinetics of orally administered furosemide.Clin. Pharmacol. Ther. 15:178–186 (1974).

    CAS  PubMed  Google Scholar 

  29. B. Beermann, E. Dalen, B. Lindstrom, and A. Rosen. On the fate of furosemide in man.Eur. J. Clin: Pharmacol. 9:57–61 (1975).

    Article  CAS  Google Scholar 

  30. B. Beermann, E. Dalen, and B. Lindstrom. Elimination of furosemide in healthy subjects and in those with renal failure.Clin. Pharmacol. Ther. 22:70–78 (1977).

    CAS  PubMed  Google Scholar 

  31. F. Andreasen, H. E. Hansen, and E. Mikkelsen. Pharmacokinetics of furosemide in anephric patients and in normal subjects.Eur. J. Clin. Pharmacol. 13:41–48 (1978).

    Article  CAS  PubMed  Google Scholar 

  32. F. Andreasen and E. Mikkelsen. Distribution, elimination and effects of furosemide in normal subjects and in patients with heart failure.Eur. J. Clin. Pharmacol. 12:15–22 (1977).

    Article  CAS  PubMed  Google Scholar 

  33. W. J. Tilstone and A. Fine. Furosemide kinetics in renal failure.Clin. Pharmacol. Ther. 23:644–650 (1978).

    CAS  PubMed  Google Scholar 

  34. D. E. Smith, D. C. Brater, E. T. Lin, and L. Z. Benet. Pharmacokinetic evaluation of the attenuation of the diuretic effect of furosemide by indomethacin in man.J. Pharmacokinet. Biopharm. (in press).

  35. A. Rane, J. P. Villeneuve, W. J. Stone, A. S. Nies, G. R. Wilkinson, and R. A. Branch. Plasma binding and disposition of furosemide in the nephrotic syndrome and in uremia.Clin. Pharmacol. Ther. 24:199–207 (1978).

    CAS  PubMed  Google Scholar 

  36. J. Honari, A. D. Blair, and R. E. Cutler. Effects of probenecid on furosemide kinetics and natriuresis in man.Clin. Pharmacol. Ther. 22:395–401 (1977).

    CAS  PubMed  Google Scholar 

  37. R. A. Branch, C. J. C. Roberts, M. Homeida, and D. Levine. Determinants of response to furosemide in normal subjects.Br. J. Clin. Pharmacol. 4:121–127 (1977).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  38. M. Homeida, C. Roberts, and R. A. Branch. Influence of probenecid and spironolactone on furosemide kinetics and dynamics in man.Clin. Pharmacol. Ther. 22:402–409 (1977).

    CAS  PubMed  Google Scholar 

  39. C.M. Huang, A. J. Atkinson, M. Levin, N. Levin, and A. Quintanilla. Pharmacokinetics of furosemide in advanced renal failure.Clin. Pharmacol. Ther. 16:659–666 (1974).

    CAS  PubMed  Google Scholar 

  40. W. A. Rupp, A. Heidland, P. HajdÚ, and G. Neuhaus. Pharmacokinetic von Furosemid bei normaler und eingeschrankter Nierenfunktion. In4. Freiburger Tagung über Nephrologie, 1970, Thieme Verlag, Stuttgart, 1971.

    Google Scholar 

  41. F. Andreasen and P. Jakobsen. Determination of furosemide in blood plasma and its binding to proteins in normal plasma and in plasma from patients with acute renal failure.Acta Pharmacol. Toxicol. 35:49–57 (1974).

    Article  CAS  Google Scholar 

  42. H. J. Rose, A. W. Pruitt, and J. L. McNay. Effect of experimental azotemia on renal clearance of furosemide in the dog.J. Pharmacol. Exp. Ther. 196:238–247 (1976).

    CAS  PubMed  Google Scholar 

  43. H. J. Rose, K. O'Malley, and A. W. Pruitt. Depression of renal clearance of furosemide in man by azotemia.Clin. Pharmacol. Ther. 21:141–146 (1976).

    Google Scholar 

  44. L. Z. Benet, A. Greither, and W. Meister. Gastrointestinal absorption of drugs in patients with cardiac failure. In L. Z. Benet (ed.),The Effect of Disease States on Drug Pharmacokinetics, APhA Academy of Pharmaceutical Sciences, American Pharmaceutical Association, Washington, D.C., 1976, pp. 33–52.

    Google Scholar 

  45. A. Greither, S. Goldman, J. S. Edelen, L. Z. Benet, and K. Cohn. Absorption of furosemide in patients with congestive heart failure.Pharmacology (in press).

  46. W. J. Tilstone and D. H. Lawson. Pharmacokinetics of furosemide in patients with heart failure.Clin. Res. 23:513A (1976).

    Google Scholar 

  47. P. HajdÚ and A. HÄussler. Untersuchungen mit dem salidiureticum 4-Chlor-N-(2-furylmethyl)-5-sulfamyl-anthranilsÄure.Arzneimittel Forsch. 14:709–710 (1964).

    Google Scholar 

  48. H. Kindt and E. Schmid. Ueber de Harnausscheidung von Furosemid bei Gesunden und Kranken mit Lebercirrhose.Pharmacol. Clin. 2:221–226 (1970).

    Article  CAS  Google Scholar 

  49. G. J. Yakatan, D. D. Maness, J. Scholler, W. J. Novick, Jr., and J. T. Doluisio. Absorption, distribution, metabolism, and excretion of furosemide in dogs and monkeys. I. Analytical methodology, metabolism, and urinary excretion.J. Pharm. Sci. 65:1456–1460 (1976).

    Article  CAS  PubMed  Google Scholar 

  50. E. Mikkelsen and F. Andreasen. Simultaneous determination of furosemide and two of its possible metabolites in biological fluids.Acta Pharmacol. Toxicol. 41:254–262 (1977).

    Article  CAS  Google Scholar 

  51. B. Lindstrom. Determination of furosemide concentrations in plasma and urine using high-speed liquid chromatography.J. Chromatog. 100:189–191 (1974).

    Article  CAS  Google Scholar 

  52. K. Carr, A. Rane, and J. C. Frölich. A simplified assay of furosemide in plasma and urine by high-pressure liquid chromatography.J. Chromatog. 145:421–427 (1978).

    Article  CAS  Google Scholar 

  53. A. D. Blair, A. W. Forrey, B. T. Meijsen, and R. E. Cutler. Assay of flucytosine and furosemide by high-pressure liquid chromatography.J. Pharm. Sci. 64:1334–1339 (1975).

    Article  CAS  PubMed  Google Scholar 

  54. E. T. Lin, D. E. Smith, L. Z. Benet, and B. A. Hoener. High-performance liquid Chromatographic assays for furosemide in plasma and urine.J. Chromatog. (submitted 1978).

  55. M. R. Kelly, A. D. Blair, A. W. Forrey, N. A. Smidt, and R. A. Cutler. A comparison of the diuretic response to oral and intravenous furosemide in “diuretic-resistant” patients.Current. Ther. Res. 21:1–9 (1977).

    CAS  Google Scholar 

  56. W. Rupp and R. M. Zapf. Beispiele zur Phase I: Diuretika.Arzneimittel Forsch. 23:1665–1668 (1973).

    CAS  Google Scholar 

  57. W. Rupp. Pharmacokinetics and pharmacodynamics of lasix.Scot. Med. J. 19:5–13 (1974).

    PubMed  Google Scholar 

  58. A. N. Brest, R. Seller, and O. Ramirez. Comparative diuretic efficacy of furosemide.J. New Drugs 5:329–332 (1965).

    Article  CAS  PubMed  Google Scholar 

  59. T. W. Wilson, K. J. Falk, J. L. Labelle, and K. B. Nguyen. Effect of dosage regimen on natriuretic response to furosemide.Clin. Pharmacol. Ther. 18:165–169 (1975).

    CAS  PubMed  Google Scholar 

  60. R. L. Galeazzi, L. Z. Benet, and L. B. Sheiner. Relationship between the pharmacokinetics and pharmacodynamics of procainamide.Clin. Pharmacol. Ther. 20:278–289 (1976).

    CAS  PubMed  Google Scholar 

  61. R. W. Schrier, D. Lehman, B. Zacherle, and L. E. Earley. Effect of furosemide on free water excretion in edematous patients with hyponatremia.Kidney Int. 3:30–34 (1973).

    Article  CAS  PubMed  Google Scholar 

  62. A. Rane, O. Oelz, J. C. Frölich, H. W. Seyberth, B. J. Sweetman, J. Throck Watson, G. R. Wilkinson, and J. A. Oates. Relation between plasma concentration of indomethacin and its effect on prostaglandin synthesis and platelet aggregation in man.Clin. Pharmacol. Ther. 23:658–668 (1978).

    CAS  PubMed  Google Scholar 

  63. J. C. Frölich, J. W. Hollifield, J. C. Dormois, B. L. Frölich, H. Seyberth, A. M. Michelakis, and J. A. Oates. Suppression of plasma renin activity by indomethacin in man.Circ. Res. 39:447–452 (1976).

    Article  PubMed  Google Scholar 

  64. R. D. Miller, R. S. Matteo, L. Z. Benet, and Y. J. Sohn. The pharmacokinetics of d-tubocurarine in man with and without renal failure.J. Pharmacol. Exp. Ther. 202:1–7 (1977).

    CAS  PubMed  Google Scholar 

  65. M. E. Allison and A. C. Kennedy. Diuretics in chronic renal disease: A study of high dosage furosemide.Clin. Sci. 41:171–187 (1971).

    CAS  PubMed  Google Scholar 

  66. N. W. Levin. Furosemide and ethacrynic acid in renal insufficiency.Med. Clin. N. Am. 55:107–120 (1971).

    CAS  PubMed  Google Scholar 

  67. R. C. Muth. Diuretic properties of furosemide in renal disease.Ann. Intern. Med. 69:249–261 (1968).

    Article  CAS  PubMed  Google Scholar 

  68. F. Cantarovich, A. Locatelli, J. C. Fernandez, J. P. Loredo, and J. Cristhot. Furosemide in high doses in the treatment of acute renal failure.Postgrad. Med. J. Suppl. 47:13–17 (1971).

    Google Scholar 

  69. L. B. Cooperman and I. L. Rubin. Toxicity of ethacrynic acid and furosemide.Am. Heart J. 85:831–834 (1973).

    Article  CAS  PubMed  Google Scholar 

  70. S. P. Rastogi, G. Volans, and R. W. Elliott. High dose furosemide in the treatment of hypertension in chronic renal insufficiency and of terminal renal failure.Postgrad. Med. J. Suppl. 47:45–53 (1971).

    Google Scholar 

  71. B. Lindstrom and M. Molander. Determination of furosemide concentrations using gas liquid chromatography.J. Chromatog. 100:189–191 (1974).

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Benet, L.Z. Pharmacokinetics/pharmacodynamics of furosemide in man: A review. Journal of Pharmacokinetics and Biopharmaceutics 7, 1–27 (1979). https://doi.org/10.1007/BF01059438

Download citation

  • Received:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01059438

Key words

Navigation