RENAL CLEARANCE OF IFOSFAMIDE

Nephrotoxicity is an important clinical side effect of the chemotherap eutic agent ifosfamide. This medication is activated by the hepatic cy tochrome P450 system with potentially toxic metabolites produced throu gh both ring hydroxylation and chloroethyl side chain oxidation pathwa ys, Using an isolated perfused rat kidney preparation, we examined the possibility that renal metabolism of ifosfamide also occurs. Renal fu nction before and after addition of ifosfamide to perfusate was not si gnificantly different. After addition of ifosfamike to the perfusate, the metabolites N2-dechloroethylifosfamide, N3-dechloroethylifosfamide , and isophasphoramide mustard were recovered from urine and renal ven ous effluent. These results provide the first demonstration of ifosfam ide metabolism by the kidney and suggest the possibility that intraten al metabolism may contribute to nephrotoxicity.