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Pharmacokinetics and metabolism of furosemide in man

European Journal of Drug Metabolism and Pharmacokinetics volume 1, pages 177–181 (1976)Cite this article

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Summary

The furosemide pharmacokinetics in healthy volunteers and in patients with renal insufficiency and hepatic cirrhosis is presented. On the average, 70 % of the oral furosemide dose is absorbed. The drug is 97.6 % bound to plasma albumins. The unbound fraction of the drug rapidly increases with albumin concentration below 2 gm per 100 ml. The half-life of furosemide ranges from 0.33 to 1.17 hours in healthy subjects, and from 4.9 to 9.7 hours in patients with advanced renal failure. In uremic patients with liver cirrhosis the elimination half-life is prolonged to more than 10 hours. Non renal clearance of furosemide is not affected by uremia; in uremic patients without liver disease about 60 to 98 % of intravenously administered dose of furosemide is excreted with bile within 24 hours. Only about 10 % of the drug is eliminated from the body during hemodialysis. The diuretic effect of furosemide is closely related to creatinine clearance: no effect in anuric cases, moderate effect if creatinine clearance is lower than 10 ml/min, and marked effect if creatinine clearance is higher than 10 ml/min 4-chloro-5-sulfamoylanthranilic acid is the only furosemide metabolite known so far. This metabolite is 1/4 as potent diuretic as the parent substance.

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References

  1. Ahmad, S., 1974, Renal insensitivity to frusemide caused by chronic anticonvulsant therapy. Brit. med. J.,3, 657–659.

    Article  CAS  PubMed  Google Scholar 

  2. Andreasen, F., Jakobsen, P., 1974, Determination of furo-semide 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.

    CAS  Google Scholar 

  3. Andreasen, F., Mikkelsen, E., 1974, The fate of furosemide in the organism of patients with cardiac incompensation. Protein binding of furosemide in the plasma from patients with cardiac disease and in normal plasma (Abstracts). Acta Pharmacol. Toxicol.,35 (suppl. I), 18.

    Google Scholar 

  4. Brauer, R. W., 1959, Mechanism of bile secretion. J. Amer. Med. Assoc.,169, 1462–1466.

    CAS  Google Scholar 

  5. Brown, C. B., Ogg, C. S., Cameron, J. S., Bewick, M., 1974, High dose frusemide in acute reversible intrinsic renal failure. Scot. med. J.,19, 35–39.

    PubMed  Google Scholar 

  6. Butler, T. C, 1971, The distribution of drugs. In Fundamentals of drug metabolism and drug disposition, ed. B. N. La Du, H. G., Mandel, E. L., Way, Williams and Wilkins, Baltimore, p. 47.

    Google Scholar 

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

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  9. Dodds, M. G., Foord, R. D., 1970, Enhancement by potent diuretics of renal tubular necrosis induced by cephaloridine. Brit. J. Pharmacol.,40, 227–236.

    CAS  Google Scholar 

  10. Epstein, M., Schneider, N. S., Befeler, B., 1975, Effect of intrarenal furosemide on renal function and intrarenal hemodynamics in acute renal failure. Amer. J. Med.,5814, 510–516.

    Article  Google Scholar 

  11. Forrey, A. W., Kimpel, B., Blair, A. D., Cutler, R. E., 1974, Furosemide concentrations in serum and urine, and its binding by serum proteins as measured fluorometrically. Clin. Chem.,20, 152–158.

    CAS  PubMed  Google Scholar 

  12. Gayer, J., 1965, Die renale Excretion des neuen Diureticum Furosemid. Klin. Wschr.,43, 898–902.

    Article  CAS  PubMed  Google Scholar 

  13. Haussler, R., Hajdu, P., 1964, Untersuchungen mit dem Salidiureticum 4-chlor-N-(2-furylmethyl)-Anthranilsaure (I, II). Arzneimittel-Forsch.,14, 709–713.

    Google Scholar 

  14. Huang, C. M., Atkinson, A. J., Levin, M., Levin, N. W., Quintanilla, A., 1974, Pharmacokinetics of furosemide in advanced renal failure. Clin. Pharmacol. Ther.,16, 659–666.

    CAS  PubMed  Google Scholar 

  15. Jacobs, C, Singlas, E., Lockmans, H., Tillement, J.-P., Simon, P., Legain, M., 1975, Recherche de la posologie optimale du furosemide chez les patients traités par dialyse itérative (submitted for publication).

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

    CAS  PubMed  Google Scholar 

  17. Kindt, H., Schmid, E., 1970, Ueber die Harnausscheidung von Furosemid bei Gesunden und Kranken mit Lebercirrhose. Pharmacologia Clinica,2, 221–226.

    Article  CAS  Google Scholar 

  18. Lawson, D. H., Tilstone, W. J., Semple, P. F., 1976, Furosemide interactions in normal volunteers. Clin. Res.,24, 510A.

    Google Scholar 

  19. Lucas, A., Meignan, M., Le Gall, J.-R., Tillement, J.-P., Rapin, M., 1976, Caractéristiques pharmacocinetiques d’une forte dose de furosémide dans l’insuffisance rénale aigue. Biomedicine,24, 45–49.

    CAS  PubMed  Google Scholar 

  20. Mitchell, J. R., Potter, W. Z., Hinson, J. A., Jollow, D. J., 1974, Hepatic necrosis caused by furosemide. Nature,251, 508–510.

    Article  CAS  PubMed  Google Scholar 

  21. Morelli, O. H., Moledo, L. I., Alanis, E., Gastori, O. L., Terzaghi, O., 1971, Acute effects of high doses of furosemide in patients with chronic renal failure, Postgrad. Med. J.,47 (suppl.), 45–53.

    Google Scholar 

  22. Nelson, W. L., Jollow, D. J., Mitchell, J. R., 1974, Mechanism of dose treshold for furosemide hepatotoxicity. Toxicol. Appl. Pharmacol.,29, 90–91.

    Google Scholar 

  23. Peters, G., Roch-Ramel, F., 1969, Furosemide. In Hand-book of Experimental Pharmacology, Springer-Verlag, Berlin,24, 386–405.

    Google Scholar 

  24. Plaa, G. L., 1971, Biliary and other routes of excretion of drugs. In Fundamentals of drug disposition and drug metabolism, ed. B. N., La Du, H. G., Mandel, E. L., Way, Williams and Wilkins, Baltimore, p. 134.

    Google Scholar 

  25. Portwich, F., Büttner, H., Schäfer, J., 1965, Simultane Untersuchung der Clearance und renalen Extraktion von Pharmaka. In Normale und patologische Funktionen des Nierentubulus. 3. Symposion der Gesellschaft fur Nephrologie, ed. K. J. u., Ullrich, K., Hierholzer, Huber, Bern, p. 173–176.

    Google Scholar 

  26. Prandota, J., Pruitt, A. W., 1975, Furosemide binding to human albumin and plasma of nephrotic children. Clin. Pharmacol. Ther.,17, 159–167.

    CAS  PubMed  Google Scholar 

  27. Prandota, J., Pruitt, A. W., 1975, Furosemide. 1. Binding to human albumin and plasma of nephrotic children. II. Pharmacokinetics, biliary excretion and metabolism in the rat. Abstracts of Vth Congress of Polish Pharmacological Society, 24–27 September, Szczecin.

  28. Prandota, J., Pruitt, A. W., 1976, Pharmacokinetic, biliary excretion and metabolic studies of14C-furosemide in the rat (submitted for publication: Proc. Soc. Exp. Biol. Med.).

  29. Reyes, E., Appelt, G. D., 1972, Pharmacological aspects of concurrent administration of furosemide and skeletal muscle relaxants.J. Pharm. Sci., 61, 562–566.

    Article  CAS  PubMed  Google Scholar 

  30. Rasmussen, L. F., Wennberg, R., 1976, Displacement of bilirubin from albumin by diuretics. Fed. Res.,10, 334.

    Google Scholar 

  31. Rupp, W., Hsidland, A., Hajdu, P., Neuhaus, G., 1970, Pharmakokinetik von Furosemid bei normaler und eingeschränkter Nierenfunktion in Medikamentöse Therapie bei Nierenerkrankungen. 4 Freiburger Tag. über Fortschritte der Nephrologie, Thieme Verlag, Stuttgart,1, p. 207.

    Google Scholar 

  32. Rupp, W., 1974, Pharmacokinetics and pharmacodynamics of Lasix. Scot. med. J.,19, 5–13.

    PubMed  Google Scholar 

  33. Seno, S., Shaw, S. M., Christian, J. E., 1969, Distribution and urinary excretion of furosemide in the rat. J. Pharm. Sci.,58, 935–938.

    Article  CAS  PubMed  Google Scholar 

  34. Tilstone, W. J., Lawson, D. H., 1976, Pharmacokinetic of furosemide in patients with heart failure. Clin. Res.,24, 513A.

    Google Scholar 

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Authors and Affiliations

  1. Clinic of Nephrology, Institute of Pediatrics, Medical Academy, 50/52 ul. M. Curie-Sklodowskiej, 50-369, Wroclaw, Poland

    J. Prandota & M. Witkowska

  2. Department of Pharmacology, Institute of Physiology and Pharmacology, Medical Academy, 50/52 ul. M. Curie-Sklodowskiej, 50-369, Wroclaw, Poland

    J. Prandota & M. Witkowska

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Prandota, J., Witkowska, M. Pharmacokinetics and metabolism of furosemide in man. European Journal of Drug Metabolism and Pharmacokinetics 1, 177–181 (1976). https://doi.org/10.1007/BF03189275

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  • DOI: https://doi.org/10.1007/BF03189275

Key-words:

  • Furosemide
  • diuretic
  • pharmacokinetics
  • metabolism man