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.
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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).
W. M. Kirkendall and J. M. Stein. Clinical pharmacology of furosemide and ethacrynic acid.Am. J. Cardiol. 22:162–167 (1968).
H. R. Jacobson and J. P. Kokko. Diuretics: Sites and mechanisms of action.Ann. Rev. Pharmacol. Toxicol. 16:201–204 (1976).
M. B. Burg. Tubular chloride transport and the mode of action of some diuretics.Kidney Int. 9:189–197 (1976).
J. F. Seely and J. H. Dirks. Site of action of diuretic drugs.Kidney. Int. 11:1–8 (1977).
M. B. Burg, L. Stoner, J. Cardinal, and N. Green. Furosemide effect on isolated perfused tubules.Am. J. Physiol. 225:119–124 (1973).
P. Deetjen. Mikropunktionsuntersuchungen zur Wirkung von Furosemide.Pflügers Arch. 284:184–190 (1965).
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).
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).
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).
J. C. McGiff, K. Crowshaw, and H. D. Itskovitz. Prostaglandins and renal function.Fed. Proc. 33:39–47 (1974).
L. M. Slotkoff. Prostaglandin A, in hypertensive crisis.Ann. Intern. Med. 81:345–347 (1974).
G. R. Zins. Renal prostaglandin.Am. J. Med. 58:14–24 (1975).
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).
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).
K. J. Stone and M. Hart. Inhibition of renal PGE2-9-ketoreductase by diuretics.Prostaglandins 12:197–207 (1976).
J. R. Paulsrud and O. N. Miller. Inhibition of 15-OH prostaglandin dehydrogenase by several diuretic drugs.Fed. Proc. 33:590 (1974).
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).
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).
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).
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).
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).
J. Gayer. Die renale Exkretion des neuen diureticum Furosemid.Klin. Wochenschr. 43:898–902 (1965).
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.
A. Haussler and P. HajdÚ. Untersuchungen mit dem salidiureticum 4-Chlor-N-(2-furylmethyl)-5-sulfamyl-anthranilsÄure.Arzneimittel-Forsch. 14:710–713 (1964).
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.
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).
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).
B. Beermann, E. Dalen, B. Lindstrom, and A. Rosen. On the fate of furosemide in man.Eur. J. Clin: Pharmacol. 9:57–61 (1975).
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).
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).
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).
W. J. Tilstone and A. Fine. Furosemide kinetics in renal failure.Clin. Pharmacol. Ther. 23:644–650 (1978).
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).
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).
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).
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).
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).
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).
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.
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).
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).
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).
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.
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).
W. J. Tilstone and D. H. Lawson. Pharmacokinetics of furosemide in patients with heart failure.Clin. Res. 23:513A (1976).
P. HajdÚ and A. HÄussler. Untersuchungen mit dem salidiureticum 4-Chlor-N-(2-furylmethyl)-5-sulfamyl-anthranilsÄure.Arzneimittel Forsch. 14:709–710 (1964).
H. Kindt and E. Schmid. Ueber de Harnausscheidung von Furosemid bei Gesunden und Kranken mit Lebercirrhose.Pharmacol. Clin. 2:221–226 (1970).
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).
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).
B. Lindstrom. Determination of furosemide concentrations in plasma and urine using high-speed liquid chromatography.J. Chromatog. 100:189–191 (1974).
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).
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).
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).
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).
W. Rupp and R. M. Zapf. Beispiele zur Phase I: Diuretika.Arzneimittel Forsch. 23:1665–1668 (1973).
W. Rupp. Pharmacokinetics and pharmacodynamics of lasix.Scot. Med. J. 19:5–13 (1974).
A. N. Brest, R. Seller, and O. Ramirez. Comparative diuretic efficacy of furosemide.J. New Drugs 5:329–332 (1965).
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).
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).
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).
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).
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).
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).
M. E. Allison and A. C. Kennedy. Diuretics in chronic renal disease: A study of high dosage furosemide.Clin. Sci. 41:171–187 (1971).
N. W. Levin. Furosemide and ethacrynic acid in renal insufficiency.Med. Clin. N. Am. 55:107–120 (1971).
R. C. Muth. Diuretic properties of furosemide in renal disease.Ann. Intern. Med. 69:249–261 (1968).
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).
L. B. Cooperman and I. L. Rubin. Toxicity of ethacrynic acid and furosemide.Am. Heart J. 85:831–834 (1973).
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).
B. Lindstrom and M. Molander. Determination of furosemide concentrations using gas liquid chromatography.J. Chromatog. 100:189–191 (1974).
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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
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DOI: https://doi.org/10.1007/BF01059438