NO TOXICITY CAUSED BY ORGAN ACCUMULATION OF CPT-11 ON MULTIPLE INJECTIONS UNDER CLINICAL REGIMENTS IN RATS

We investigated the accumulation of CPT-11 and its metabolite(SN-38)in various organs and toxicities on multiple injections of CPT-11 under clinical regiments in SD rats. CPT-11(16.7 mg/kg equivalent to 100 mg/m2)was administered intravenously by a single injection, or by multiple injections in 1 course(once a week for three consecutive weeks)or 3 courses(1 course repeated 3 times at intervals of 2 weeks). There was no tendency for CPT-11 and SN-38 to accumulate in any organs regardless of the number of injections. Treatment-related changes were not observed in the general condition, body weight, hematology, biochemistry, and organ weights. Histopathological changes induced by CPT-11 were not persistent and the rats made a rapid recovery after the administrations. From these results, it is suggested that there is no toxicity caused by accumulation of CPT-11 and its active metabolite, SN-38, in organs under clinical regiments in rats.