Nephrotoxicity and pharmacokinetics of cisplatinum in young and adult rats

Wistar rats (10 and 55 days old) were administered a single dose of 0.6 mg cisplatinum (CP) 100 g body wt. intraperitoneally. Urinary volume, p-aminohippurate and total protein excretion were determined. Separation of urinary proteins was performed by sodium dodecylsulfate polyacrylamide gel electrophoresis. Significant symptoms of nephrotoxicity (oliguria, reduced PAH-excretion, heavy proteinuria, changes in urinary protein composition) were detected in adult rats 72 h after CP. At that time young rats did not show distinct signs of nephrotoxicity. Experiments on time dependence of nephrotoxicity showed that in young rats symptoms occurred already 6 h after CP-administration, and 72 h after CP the damage was nearly completely repaired. Pt-determination in serum, kidney tissue, and urine showed a shorter t1/2 in serum, lower concentrations in kidney tissue as well as higher Pt-concentrations in urine of young compared with adult rats.