Abstract
The effect of furosemide on gentamicin excretion and tissue accumulation was studied with clearance techniques in anesthetized rats, at two different infusion rates of saline or Ringer solution. Gentamicin (∼20 mg/kg) was administered by constant intravenous infusion over a period of 3 h. With the low fluid infusion rate, furosemide (25 mg/kg intravenously) caused severe reduction in glomerular filtration rate and diminished urinary output of gentamicin. Serum and renal tissue levels of the antibiotic were significantly elevated. High fluid infusion prevented the decline of the glomerular filtration rate, with near normalization of all measurements. A fluid deficit incurred by furosemide was noted at both the low and high infusion rates. Complete correction of this fluid deficit by continuous adjustment of the infusion rate fully restored normal renal handling of gentamicin. These results suggest that furosemide had no direct effect on renal excretion of gentamicin. In comparison, renal handling of gentamicin in rats did not respond to changes in the rate of fluid infusion in the absence of furosemide therapy. It appears that gentamicin excretion and gentamicin accumulation in the renal cortex in furosemide-treated rats, in contrast with those in untreated rats, are influenced significantly by the rate of fluid infusion. Fluid administration sufficient to maintain the glomerular filtration rate was found to be necessary for appropriate gentamicin elimination, with consequent reduction in serum and renal tissue levels of the drug.
Full text
PDF
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Burke T. J., Robinson R. R., Clapp J. R. Determinants of the effect of furosemide on the proximal tubule. Kidney Int. 1972;1(1):12–18. doi: 10.1038/ki.1972.3. [DOI] [PubMed] [Google Scholar]
- Chiu P. J., Brown A., Miller G., Long J. F. Renal extraction of gentamicin in anesthetized dogs. Antimicrob Agents Chemother. 1976 Aug;10(2):277–282. doi: 10.1128/aac.10.2.277. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gordon R. C., Regamey C., Kirby W. M. Serum protein binding of the aminoglycoside antibiotics. Antimicrob Agents Chemother. 1972 Sep;2(3):214–216. doi: 10.1128/aac.2.3.214. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Greenblatt D. J., Duhme D. W., Allen M. D., Koch-Weser J. Clinical toxicity of furosemide in hospitalized patients. A report from the Boston Collaborative Drug Surveillance Program. Am Heart J. 1977 Jul;94(1):6–13. doi: 10.1016/s0002-8703(77)80337-2. [DOI] [PubMed] [Google Scholar]
- Jewkes R. F., Burki N., Guz A. Observations of renal function in patients undergoing therapeutic diuresis with frusemide. Clin Sci. 1970 Apr;38(4):439–449. doi: 10.1042/cs0380439. [DOI] [PubMed] [Google Scholar]
- Luft F. C., Kleit S. A. Renal parenchymal accumulation of aminoglycoside antibiotics in rats. J Infect Dis. 1974 Dec;130(6):656–659. doi: 10.1093/infdis/130.6.656. [DOI] [PubMed] [Google Scholar]
- Luft F. C., Patel V., Yum M. N., Kleit S. A. Nephrotoxicity of cephalosporin-gentamicin combinations in rats. Antimicrob Agents Chemother. 1976 May;9(5):831–839. doi: 10.1128/aac.9.5.831. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Tilstone W. J., Semple P. F., Lawson D. H., Boyle J. A. Effects of furosemide on glomerular filtration rate and clearance of practolol, digoxin, cephaloridine, and gentamicin. Clin Pharmacol Ther. 1977 Oct;22(4):389–394. doi: 10.1002/cpt1977224389. [DOI] [PubMed] [Google Scholar]
- Wahlig H., Metallinos A., Hameister W., Bergmann R. Gentamycin-Konzentrationen in Geweben und Körperflüssigkeiten von Versuchstieren. Int J Clin Pharmacol. 1974 Oct;10(3):212–219. [PubMed] [Google Scholar]
- Whelton A., Walker W. G. Editorial: Intrarenal antibiotic distribution in health and disease. Kidney Int. 1974 Sep;6(3):131–137. doi: 10.1038/ki.1974.91. [DOI] [PubMed] [Google Scholar]