Metabolism of bumetanide
The metabolism of bumetanide is reviewed, with emphasis on the relationship between metabolism and diuretic activity. Substantial evidence has been obtained for the thesis that diuretic activity is dependent on the amount of bumetanide which reaches the renal tubule. Therefore, bumetanide is a potent diuretic in those species, in which a substantial fraction of the administered dose is excreted as unchanged drug in the urine. In contrast, relatively weak diuretic activity is seen in the rat, a species which very effectively biotransforms bumetanide to inactive metabolites. The metabolites which have been identified in human and rat urine are presented, and the point is made that in both species metabolism of bumetanide appears to be limited to oxidation of the N-butyl side chain. Different (and unidentified) metabolites are excreted by the dog. A prominent metabolite formed in the dog, however, is the acylglucuronide of bumetanide, which was detected in plasma and bile but was not seen in urine or feces. Tissue distribution of bumetanide in the dog is presented so as to show the ability of the kidney to concentrate bumetanide. In the human, bumetanide disposition is also characterized by 95 per cent plasma protein binding and a plasma half-life of 1 to 2 hours. Attention is given to the possibility that the clinical response to bumetanide can be altered by factors which affect drug oxidation by the mixed-function oxygenase system.
- Research Organization:
- Department of Biochemistry, Hoffmann-LaRoche, Inc., Nutley, NJ
- OSTI ID:
- 6933097
- Journal Information:
- J. Clin. Pharmacol.; (United States), Journal Name: J. Clin. Pharmacol.; (United States) Vol. 21:11-12 Pt 2; ISSN JCPCB
- Country of Publication:
- United States
- Language:
- English
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59 BASIC BIOLOGICAL SCIENCES
ANIMALS
BINDING ENERGY
BIOLOGICAL EFFECTS
BIOLOGICAL MATERIALS
BIOLOGICAL WASTES
BLOOD
BLOOD PLASMA
BODY FLUIDS
CARBON 14 COMPOUNDS
CHEMICAL ANALYSIS
DETOXIFICATION
DISTRIBUTION
DOGS
DRUGS
ENERGY
ENZYME ACTIVITY
LABELLED COMPOUNDS
MAMMALS
MATERIALS
METABOLISM
METABOLITES
QUANTITATIVE CHEMICAL ANALYSIS
QUANTITY RATIO
TIME DEPENDENCE
TISSUE DISTRIBUTION
URINE
VERTEBRATES
WASTES