Nephrotoxicity of cis-platin comparing young and adult rats

The effect of Cis-platin on the glomerular filtration rate and effective renal plasma flow was determined using a radioisotope clearance technique in young (3 wk old) and adult (more than 12 wk old) rats. Cis-platin was administered intravenously in dosages ranging from 2.5 to 10 mg/kg body weight, either as a single dose or fractionated over 5 consecutive days. Following either dose regimen, identical total doses of Cis-platin caused less severe nephrotoxicity in young rats than in adult ones. In adult rats fractionated dosage significantly reduced nephrotoxicity. This was not observed in young rats. The difference in nephrotoxicity between young and adult rats was due to the renal handling of Cis-platin. After a single dose of 5 and 7.5 mg/kg body weight, platinum concentrations were measured in urine and renal tissue. During the first 2 days after Cis-platin administration, up to 60% of the amount of platinum injected was excreted in the urine of both age groups. There was a marked difference, however, in renal platinum concentration between the two groups. In young rats renal platinum concentration was only 63 and 49% of that in adult rats after 5 and 7.5 mg/kg body weight, respectively. We believe that this is due to the comparatively larger renal mass in relation to body weight in the young animals. Relatively more renal tissue provides at least partial protection against nephrotoxic drugs in these young rats.