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.

[1]  W. Flamenbaum,et al.  Pharmacology, Therapeutic Efficacy, and Adverse Effects of Bumetanide, A New “Loop” Diuretic , 1982, Pharmacotherapy.

[2]  D. Brater,et al.  Pharmacokinetic-dynamic analysis of the indomethacin-furosemide interaction in man. , 1980, The Journal of pharmacology and experimental therapeutics.

[3]  D. Brater Pharmacodynamic considerations in the use of diuretics. , 1983, Annual review of pharmacology and toxicology.

[4]  A. Fine,et al.  Furosemide kinetics in renal failure , 1978, Clinical pharmacology and therapeutics.

[5]  K. Alexander,et al.  Bumetanide: radioimmunoassay and pharmacokinetic profile in humans. , 1976, Journal of pharmaceutical sciences.

[6]  L. Ramsay,et al.  Bumetanide and frusemide: a comparison of dose-response curves in healthy men. , 1978, British journal of clinical pharmacology.

[7]  B. Odlind Relation between renal tubular secretion and effects of five loop diuretics. , 1979, The Journal of pharmacology and experimental therapeutics.

[8]  G. Dehmer,et al.  Absorption and disposition of furosemide in congestive heart failure. , 1982, Kidney international.

[9]  B. Beermann,et al.  Elimination of furosemide in healthy subjects and in those with renal failure , 1977, Clinical pharmacology and therapeutics.

[10]  W. M. Kirby,et al.  Laboratory and clinical studies of penicillin X‐1497 , 1961, Clinical pharmacology and therapeutics.

[11]  K. O’malley,et al.  Depression of renal clearance of furosemide in man by azotemia , 1977, Clinical pharmacology and therapeutics.

[12]  D. Brater,et al.  The time course of delivery of furosemide into urine: an independent determinant of overall response. , 1982, Kidney international.

[13]  G. Skellern,et al.  Determination of the diuretic bumetanide in biological fluids by high-performance liquid chromatography. , 1980, Journal of chromatography.

[14]  L. Benet,et al.  Absorption and disposition of furosemide in healthy volunteers, measured with a metabolite-specific assay. , 1980, Drug metabolism and disposition: the biological fate of chemicals.

[15]  D. Brater,et al.  Pharmacodynamic analysis of the furosemide-probenecid interaction in man. , 1979, Kidney international.

[16]  P. Neuvonen,et al.  Fate of [14C]-bumetanide in man. , 1977, British journal of clinical pharmacology.

[17]  D. Brater,et al.  Bumetanide and furosemide , 1983, Clinical pharmacology and therapeutics.

[18]  R. Cutler,et al.  Clinical Pharmacokinetics of Frusemide , 1979, Clinical pharmacokinetics.

[19]  D. Brater,et al.  Furosemide in patients with heart failure: Shift in dose‐response curves , 1980, Clinical pharmacology and therapeutics.

[20]  D. Davies,et al.  Renal action, therapeutic use, and pharmacokinetics of the diuretic bumetanide , 1974, Clinical pharmacology and therapeutics.

[21]  A. Forrey,et al.  Pharmacokinetics of furosemide in normal subjects and functionally anephric patients , 1974, Clinical pharmacology and therapeutics.

[22]  J. Villeneuve,et al.  Plasma binding and disposition of furosemide in the nephrotic syndrome and in uremia , 1978, Clinical pharmacology and therapeutics.

[23]  J. Wagner,et al.  CSTRIP, a fortran IV computer program for obtaining initial polyexponential parameter estimates. , 1976, Journal of pharmaceutical sciences.

[24]  A. Done The nature of the antirheumatic action of salicylates , 1960, Clinical pharmacology and therapeutics.