Abstract
We compared the nephrotoxic interaction between cisplatin (CP) and amikacin (AM) in young and adult rats, using different dosage combinations. Following a single i.v. dose of CP, AM was administered s. c. for 14 days. The dose of CP was chosen to cause a 20%–50% fall in the glomerular filtration rate (GFR), while a dose of AM was chosen that had only a minimal effect on GFR. In adult rats, a decrease in GFR to 60% of the control value after CP alone was seriously aggravated by a non-toxic AM course given during 2 weeks after CP. In this combination, the GFR per 100 g body weight was reduced to 30% of control at week 2, which rose to 40% of control at week 15. In young rats, a non-toxic AM course did not aggravate the CP-induced impairment in GFR. However, when the dose of AM was increased to cause a 20% reduction in the GFR, the nephrotoxicity was potentiated. When measured at week 2, the GFR per 100 g body weight was 40% of control after the combined treatment compared with 80% of control after CP alone. As in adult rats, there was only a partial recovery of the GFR. In conclusion, in both adult and young rats, a course of AM following a single injection of CP potentiated CP-induced nephrotoxicity.
Similar content being viewed by others
References
Provoost AP, Adejuyigbe O, Wolff ED (1985) Nephrotoxicity of aminoglycosides in young and adult rats. Pediatr Res 19: 1191–1196
Jongejan HTM, Provoost AP, Wolff ED, Molenaar JC (1986) Nephrotoxicity of Cis-platin comparing young and adult rats. Pediatr Res 20: 9–14
Haas A, Anderson L, Lad T (1983) The influence of aminoglycosides on the nephrotoxicity of Cis-diamminedichloroplatinum in cancer patients. J Infect Dis 147:363
Gonzalez-Vitale JC, Hayes DM, Cvitkovic E, Sternberg SS (1978) Acute renal failure after cis-Dichlorodiammine-platinum (II) and gentamicin-cephalothin therapies. Cancer Treat Rep 62: 693–698
Elliott WC, Houghton DC, Gilbert DN, Baines-Hunter J, Bennett WM (1982) Gentamicin nephrotoxicity. II. Definition of conditions necessary to induce acquired insensitivity. J Lab Clin Med 100: 513–525
Luft FC, Yum MN, Kleit SA (1977) The effect of concomitant mercuric chloride and gentamicin on kidney function and structure in the rat. J Lab Clin Med 89: 622–631
Elliott WC, Houghton DC, Gilbert DN, Baines-Hunter J, Bennett WM (1982) Gentamicin nephrotoxicity. I. Degree and permanence of acquired insensitivity. J Lab Clin Med 100: 501–512
Kawamura J, Soeda A, Yoshida O (1981) Nephrotoxicity of Cis-diamminechloroplatinum (II) (Cis-platinum) and the additive effect of antibiotics: morphological and functional observation in rats. Toxicol Appl Pharmacol 58: 475–482
Bregman CL, Williams PD (1986) Comparative nephrotoxicity of carboplatin and cisplatin in combination with tobramycin. Cancer Chemother Pharmacol 18: 117–123
Provoost AP, De Keijzer MH, Wolff ED, Molenaar JC (1983) Development of renal function in the rat. Renal Physiol 6: 1–9
Dobyan DC, Levi J, Jacobs C, Kosek J, Weiner MW (1980) Mechanism of Cis-platinum nephrotoxicity. II. Morphologic observations. J Pharmacol Exp Ther 213: 551–556
Chopra S, Kaufman JS, Jones TW, Hong WK, Gehr MK, Hamburger RJ, Flamenbaum W, Trump BF (1982) Cis-diamminedichloroplatinum-induced acute renal failure in the rat. Kidney Int 21: 54–64
Choie DD, Longnecker DS, Del Campo AA (1981) Acute and chronic Cisplatin nephropathy in rats. Lab Invest 44: 397–402
Goldstein RS, Mayor GH (1983) The nephrotoxicity of Cisplatin. Life Sci 32: 685–690
Whelton A (1982) Renal tubular transport and intrarenal aminoglycoside distribution. In: Whelton A, Neu HC (eds) The aminoglycosides. Dekker, New York, pp 191–222
Gilbert DN, Houghton DC, Bennett WM, Plamp CE, Reger K, Porter GA (1979) Reversibility of gentamicin nephrotoxicity in rats: recovery during continuous drug administration. Proc Soc Exp Biol Med 160: 99–103
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Jongejan, H.T.M., Provoost, A.P. & Molenaar, J.C. Potentiated nephrotoxicity of cisplatin when combined with amikacin comparing young and adult rats. Pediatr Nephrol 3, 290–295 (1989). https://doi.org/10.1007/BF00858533
Received:
Revised:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00858533