| Autor: |
Slatter, John Greg, Schaaf, Larry J., Sams, James P., Feenstra, Kenneth L., Johnson, Mark G., Bombardt, Paul A., Cathcart, Karen Sue, Verburg, Michael T., Pearson, Laura K., Compton, Linda D., Miller, Langdon L., Baker, David S., Pesheck, Caroline V., Lord, Raymond S. |
| Zdroj: |
Drug Metabolism and Disposition; April 2000, Vol. 28 Issue: 4 p423-433, 11p |
| Abstrakt: |
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. |
| Databáze: |
Supplemental Index |
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