947 CPT–11 Metabolism in blood, bile and urine in cancer patients

CPT-11 (Irinotecan) is a water soluble semisynthetic derivative of camptothecin. It acts as an inhibitor of DNA topoisomerase I. Two patients were treated with CPT-11 for colorectal cancer. Both of them had a biliary catheter for extrahepatic biliary obstruction. The 1st patient received CPT-11 on a 100 mg/m 2 weekly schedule and the second was administered 350 mg/m 2 every 3 weeks. In plasma, the active identified metabolite SN-38 was mainly in the form of a glucuronide conjugate (ratio: 1 to 4 for 100 mg/m 2 and I to 12 for 350 mg/m 2 . CPT-11 was mainly excreted in bile and urine as CPT-II. Cumulative biliary and urinary excretion of CPT-11 and its metabolites over a period of time up to 48 hours was 25% (100 mg/m 2 weekly) to 50% (350 mg/m 2 every 3 weeks). This means that CPT-11 might be excreted in other not yet identified forms.