PT  - JOURNAL ARTICLE
AU  - John Greg Slatter
AU  - Larry J. Schaaf
AU  - James P. Sams
AU  - Kenneth L. Feenstra
AU  - Mark G. Johnson
AU  - Paul A. Bombardt
AU  - Karen Sue Cathcart
AU  - Michael T. Verburg
AU  - Laura K. Pearson
AU  - Linda D. Compton
AU  - Langdon L. Miller
AU  - David S. Baker
AU  - Caroline V. Pesheck
AU  - Raymond S. Lord III
TI  - Pharmacokinetics, Metabolism, and Excretion of Irinotecan (CPT-11) Following I.V. Infusion of [<sup>14</sup>C]CPT-11 in Cancer Patients
DP  - 2000 Apr 01
TA  - Drug Metabolism and Disposition
PG  - 423--433
VI  - 28
IP  - 4
4099  - http://dmd.aspetjournals.org/content/28/4/423.short
4100  - http://dmd.aspetjournals.org/content/28/4/423.full
SO  - Drug Metab Dispos2000 Apr 01; 28
AB  - This study determined the disposition of irinotecan hydrochloride trihydrate (CPT-11) after i.v. infusion of 125 mg/m2 (100 μCi) [14C]CPT-11 in eight 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. Radioactivity in blood, plasma, urine, and feces was determined for at least 168 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 excreted 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 urine, bile, and feces. Aminopentane carboxylic acid (APC) and SN-38 glucuronide (SN-38G) were the most significant metabolites in urine and bile, whereas SN-38 and NPC, a primary amine metabolite, were relatively minor excretion 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 presumably due to hydrolysis of SN-38G to SN-38 by enteric bacterial β-glucuronidases. There was close correspondence between quantitative fluorescence HPLC and mass balance findings. CPT-11 was the major circulating component in 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. These results show that the parent drug and its three major metabolites account for virtually all CPT-11 disposition, with fecal excretion representing the major elimination pathway. The American Society for Pharmacology and Experimental Therapeutics