Abstract
We compared the nephrotoxicity and renal accumulation of two aminoglycosides, Gentamicin (Gra) and Amikacin (Ak), and of Cisplatin (Cp) in young (BW ±50g) and adult (BW ±300g) rats. The glomerular filtration rate (GFR) was measured regularly as the plasma clearance of Cr-51 EDTA, with a method allowing repeated use within the same animal. The aminoglycosides were administered s.c. for 14 days (60mg Gm and 180mg Ak per kg/day). Cp was given as a single i.v. injection (5mg/kg). Measurements of the acute effects of the drugs, i.e. on day 14 for the aminoglycosides and on day 4 for Cp, revealed that the decrease in GFR was significantly less in young rats than in adults for all drugs. The GFR recovered completely in the young, while a permanent impairment remained in adult rats treated with Gm or Cp. Measurement of renal drug levels showed that these were significantly lower in young rats than in adults. This was not due to a diminished uptake (as a % of the injected amount), but to the heigh kidney weight relative to body weight in young rats. Per 100g BW the wet kidney weight of young rats was 190% of that in adults. The renal drug concentration in young rats was in average only 55% of that in adult, rats. We conclude that if 1) drugs are administered relative to BW and 2) they have to accumulate in the kidney to become nephrotoxic, the young rats are at least partially protected because of their high relative kidney weight.
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Jongejan, H., Provoost, A., Adejuyigbe, O. et al. 84 IS THE YOUNG RAT PROTECTED TO NEPHROTOXIC DRUGS BY ITS HIGH KIDNEY WEIGHT RELATIVE TO BODY WEIGHT?. Pediatr Res 20, 1047 (1986). https://doi.org/10.1203/00006450-198610000-00138
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DOI: https://doi.org/10.1203/00006450-198610000-00138