Pharmacokinetics, metabolism, and excretion of irinotecan (CPT-11) following i.v. infusion of [C-14]CPT-11 in cancer patients

This study determined the disposition of irinotecan hydrochloride trihydrat e (CPT-11) after i.v. infusion of 125 mg/m(2) (100 mu Ci) [C-14]CPT-11 in e ight patients with solid tumors. Mean +/- S.D. recovery of radioactivity in urine and feces was 95.8 +/- 2.7% (range 92.2-100.3%, n = 7) of dose. Radi oactivity in blood, plasma, urine, and feces was determined for at least 16 8 h after dosing. Fecal excretion accounted for 63.7 +/- 6.8 (range 54.2-74 .9%, n = 7) of dose, whereas urinary excretion accounted for 32.1 +/- 6.9% (range 21.7-43.8%; n = 7) of dose. One patient with a biliary T-tube excret ed 30.1% of dose in bile, 14.2% in feces, and 48.2% in urine. Quantitative radiometric HPLC revealed that CPT-11 was the major excretion product in ur ine, bile, and feces. Aminopentane carboxylic acid (APC) and SN-38 glucuron ide (SN-38G) were the most significant metabolites in urine and bile, where as SN-38 and NPC, a primary amine metabolite, were relatively minor excreti on products. SN-38 and APC were the most significant metabolites in feces. The relatively higher amount of SN-38 in feces compared with bile is presum ably due to hydrolysis of SN-38G to SN-38 by enteric bacterial beta-glucuro nidases. There was close correspondence between quantitative fluorescence H PLC and mass balance findings. CPT-11 was the major circulating component i n plasma (55% of the mean radiochemical area under the curve), and CPT-11, SN-38, SN-38G, and APC accounted for 93% of the mean radiochemical AUC. The se results show that the parent drug and its three major metabolites accoun t for virtually all CPT-11 disposition, with fecal excretion representing t he major elimination pathway.