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. 1980 Jul;18(1):176–181. doi: 10.1128/aac.18.1.176

Comparative low-dose nephrotoxicities of gentamicin, tobramycin, and amikacin.

G H Hottendorf, L L Gordon
PMCID: PMC283960  PMID: 7416743

Abstract

Most investigations of the comparative nephrotoxicities of aminoglycosides in animals have utilized large multiples of the human dose. Furthermore, many of these assessments have used only one or two dose levels and have not described a dose-response comparison among antibiotics. Because of this lack of comparative dose-response data over a range of low multiples of the human dose, the nephrotoxicities of gentamicin, tobramycin, and amikacin were investigated in 180 rats, utilizing doses ranging from one to seven times the equivalent human clinical doses. Histopathological evaluations of both kidneys from each rat were scored without knowledge of the treatment, and statistical analyses of the results indicated that a linear and parallel dose-response relationship existed for each drug, the relative nephrotoxicity over the range of doses analyzed was gentamicin > tobramycin > amikacin (P = 0.0001), and, unlike amikacin, the human dose equivalents (milligrams per kilogram) of gentamicin and tobramycin were significantly nephrotoxic in rats (P < 0.05).

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Appel G. B., Neu H. C. Gentamicin in 1978. Ann Intern Med. 1978 Oct;89(4):528–538. doi: 10.7326/0003-4819-89-4-528. [DOI] [PubMed] [Google Scholar]
  2. BERLYNE G. M., VARLEY H., NILWARANGKUR S., HOERNI M. ENDOGENOUS-CREATININE CLEARANCE AND GLOMERULAR-FILTRATION RATE. Lancet. 1964 Oct 24;2(7365):874–876. doi: 10.1016/s0140-6736(64)90735-4. [DOI] [PubMed] [Google Scholar]
  3. Barza M., Pinn V., Tanguay P., Murray T. Nephrotoxicity of newer cephalosporins and aminoglycosides alone and in combination in a rat model. J Antimicrob Chemother. 1978 May;4 (Suppl A):59–68. doi: 10.1093/jac/4.suppl_a.59. [DOI] [PubMed] [Google Scholar]
  4. Baum N., Dichoso C. C., Carlton C. E. Blood urea nitrogen and serum creatinine. Physiology and interpretations. Urology. 1975 May;5(5):583–588. doi: 10.1016/0090-4295(75)90105-3. [DOI] [PubMed] [Google Scholar]
  5. Beck H., Züllich B., Marre R., Sack K. Tierexperimentelle Untersuchungen zur Nephrotoxizität von 7 Aminoglykosiden bei Langzeitbehandlung. Arzneimittelforschung. 1979;29(6):935–939. [PubMed] [Google Scholar]
  6. Cronin R. E. Aminoglycoside nephrotoxicity: pathogenesis and prevention. Clin Nephrol. 1979 May;11(5):251–256. [PubMed] [Google Scholar]
  7. Cuppage F. E., Setter K., Sullivan P., Reitzes E. J., Melnykovych A. O. Gentamicin nephrotoxicity. II. Physiological, biochemical and morphological effects of prolonged administration to rats. Virchows Arch B Cell Pathol. 1977 Jun 24;24(2):121–138. [PubMed] [Google Scholar]
  8. Dossetor J. B. Creatininemia versus uremia. The relative significance of blood urea nitrogen and serum creatinine concentrations in azotemia. Ann Intern Med. 1966 Dec;65(6):1287–1299. doi: 10.7326/0003-4819-65-6-1287. [DOI] [PubMed] [Google Scholar]
  9. Gilbert D. N., Houghton D. C., Bennett W. M., Plamp C. E., Reger K., Porter G. A. Reversibility of gentamicin nephrotoxicity in rats: recovery during continuous drug administration. Proc Soc Exp Biol Med. 1979 Jan;160(1):99–103. doi: 10.3181/00379727-160-40397. [DOI] [PubMed] [Google Scholar]
  10. Gilbert D. N., Plamp C., Starr P., Bennet W. M., Houghton D. C., Porter G. Comparative nephrotoxicity of gentamicin and tobramycin in rats. Antimicrob Agents Chemother. 1978 Jan;13(1):34–40. doi: 10.1128/aac.13.1.34. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Hewitt W. L. The cephalosporins--1973. J Infect Dis. 1973 Oct;128(Suppl):S312–S319. doi: 10.1093/infdis/128.supplement_2.s312. [DOI] [PubMed] [Google Scholar]
  12. Kosek J. C., Mazze R. I., Cousins M. J. Nephrotoxicity of gentamicin. Lab Invest. 1974 Jan;30(1):48–57. [PubMed] [Google Scholar]
  13. Luft F. C. Netilmicin: a review of toxicity in laboratory animals. J Int Med Res. 1978;6(4):286–299. doi: 10.1177/030006057800600406. [DOI] [PubMed] [Google Scholar]
  14. Luft F. C., Rankin L. I., Sloan R. S., Yum M. N. Recovery from aminoglycoside nephrotoxicity with continued drug administration. Antimicrob Agents Chemother. 1978 Sep;14(3):284–287. doi: 10.1128/aac.14.3.284. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. MILLER B. F., LEAF A., MAMBY A. R., MILLER Z. Validity of the endogenous creatinine clearance as a measure of glomerular filtration rate in the diseased human kidney. J Clin Invest. 1952 Mar;31(3):309–313. doi: 10.1172/JCI102607. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Pechere J. C., Dugal R. Clinical pharmacokinetics of aminoglycoside antibiotics. Clin Pharmacokinet. 1979 May-Jun;4(3):170–199. doi: 10.2165/00003088-197904030-00002. [DOI] [PubMed] [Google Scholar]
  17. Reiner N. E., Bloxham D. D., Thompson W. L. Nephrotoxicity of gentamicin and tobramycin given once daily or continuously in dogs. J Antimicrob Chemother. 1978 May;4 (Suppl A):85–101. doi: 10.1093/jac/4.suppl_a.85. [DOI] [PubMed] [Google Scholar]
  18. SHARRATT M., FRAZER A. C. The sensitivity of function tests in detecting renal damage in the rat. Toxicol Appl Pharmacol. 1963 Jan;5:36–48. doi: 10.1016/0041-008x(63)90080-2. [DOI] [PubMed] [Google Scholar]
  19. Sairio E., Kasanen A., Kangas L., Nieminen A. L., Nieminen L. The nephrotoxicity and renal accumulation of amikacin, tobramycin and gentamycin in rats, rabbits and guinea pigs. Exp Pathol (Jena) 1978;15(6):370–375. doi: 10.1016/s0014-4908(78)80045-3. [DOI] [PubMed] [Google Scholar]
  20. Schentag J. J., Gengo F. M., Plaut M. E., Danner D., Mangione A., Jusko W. J. Urinary casts as an indicator of renal tubular damage in patients receiving aminoglycosides. Antimicrob Agents Chemother. 1979 Oct;16(4):468–474. doi: 10.1128/aac.16.4.468. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Soberon L., Bowman R. L., Pastoriza-Munoz E., Kaloyanides G. J. Comparative nephrotoxicities of gentamicin, netilmicin and tobramycin in the rat. J Pharmacol Exp Ther. 1979 Sep;210(3):334–343. [PubMed] [Google Scholar]
  22. Stroo W. E., Hook J. B. Enzymes of renal origin in urine as indicators of nephrotoxicity. Toxicol Appl Pharmacol. 1977 Mar;39(3):423–434. doi: 10.1016/0041-008x(77)90135-1. [DOI] [PubMed] [Google Scholar]
  23. Welles J. S., Emmerson J. L., Gibson W. R., Nickander R., Owen N. V., Anderson R. C. Preclinical toxicology studies with tobramycin. Toxicol Appl Pharmacol. 1973 Jul;25(3):398–409. doi: 10.1016/0041-008x(73)90313-x. [DOI] [PubMed] [Google Scholar]
  24. Wellwood J. M., Lovell D., Thompson A. E., Tighe J. R. Renal damage caused by gentamicin: a study of the effects on renal morphology and urinary enzyme excretion. J Pathol. 1976 Mar;118(3):171–182. doi: 10.1002/path.1711180307. [DOI] [PubMed] [Google Scholar]
  25. Whelton A., Carter G. G., Craig T. J., Bryant H. H., Herbst D. V., Walker W. G. Comparison of the intrarenal disposition of tobramycin and gentamicin: therapeutic and toxicologic answers. J Antimicrob Chemother. 1978 May;4 (Suppl A):13–22. doi: 10.1093/jac/4.suppl_a.13. [DOI] [PubMed] [Google Scholar]
  26. Wright P. J., Plummer D. T. The use of urinary enzyme measurements to detect renal damage caused by nephrotoxic compounds. Biochem Pharmacol. 1974 Jan 1;23(1):65–73. doi: 10.1016/0006-2952(74)90314-1. [DOI] [PubMed] [Google Scholar]

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