Furosemide disposition in cirrhosis

@article{Verbeeck1982FurosemideDI,
  title={Furosemide disposition in cirrhosis},
  author={Roger K. Verbeeck and Rashmi V. Patwardhan and Jean-Pierre Villeneuve and Grant R. Wilkinson and Robert A. Branch},
  journal={Clinical Pharmacology \& Therapeutics},
  year={1982},
  volume={31}
}
Furosemide disposition after rapid intravenous injection (80 mg) was studied in 10 normal healthy subjects and eight patients with cirrhosis and ascites. In the cirrhotic patients the elimination half‐life was modestly longer (81.0 ± 8.0 min and 60.2 ± 5.8 min). This prolongation was not associated with a difference in systemic clearance (156 ± 7 ml/min in normal and 142 ± 16 ml/min in cirrhotic subjects), rather it was a reflection of alterations in furosemide distribution. The steady‐state… 
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References

SHOWING 1-10 OF 17 REFERENCES
Elimination of furosemide in healthy subjects and in those with renal failure
TLDR
Although the furosemide plasma t½ was essentially normal, the elimination rate of metabolites was decreased and the main route of excretion of label was in the feces, unlike that of healthy subjects.
Disposition of furosemide in functionally hepatectomized dogs.
TLDR
It is demonstrated that, although nonrenal clearance accounts for about 50% of the elimination of furosemide, the liver does not play a significant role in this process in the dog.
Pharmacokinetics of furosemide in advanced renal failure
TLDR
Diuretic response was always less after oral than after intravenous furosemide, and the slow, intravenous infusion of this drug is recommended for maximal efficacy in uremic patients.
Biotransformation of furosemide in patients with acute pulmonary edema.
TLDR
Urinary excretion of furosemide was less in patients with, than in those without, myocardial infarction and the glucuronide metabolite was the major biotransformation product in these patients with acute pulmonary edema.
Renal secretion of [35-S]furosemide and depression by albumin binding.
  • R. H. Bowman
  • Medicine, Biology
    The American journal of physiology
  • 1975
TLDR
It is concluded that at physiological albumin concentrations, a very small fraction of circulating furosemide will be available for filtration, and tubular-fluid and urinary furoSemide will arise predominantly from secretion.
FACTORS AFFECTING DRUG METABOLISM
  • J. Gillette
  • Biology
    Annals of the New York Academy of Sciences
  • 1971
TLDR
It has become increasingly evident that most of the oxidative reactions are catalyzed by enzyme systems in liver endoplasmic reticulum, which is disrupted by homogenization to form microsomes, and the diversity of the reactions catalyzing by these enzymes is virtually unique in biochemistry.
A physiological approach to hepatic drug clearance
TLDR
The proposed classification of drug metabolism based on the hepatic extraction ratio allows prediction and interpretation of the effects of individual variations in drug‐metabolizing activity, route of administration, pharmacokinetic interactions, and disease states on hepatic drug elimination.
Plasma binding and disposition of furosemide in the nephrotic syndrome and in uremia
TLDR
It is indicated that the disposition of furosemide is not only dependent on renal function but also on the serum albumin concentration.
Plasma and tissue binding of drugs in pharmacokinetics
  • Drug Metab Rev
  • 1976
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