Characterization of CPT-11 converting carboxylesterase activity in colon tumor and normal tissues: comparison with p-nitro-phenylacetate converting carboxylesterase activity

Anticancer Drugs. 2000 Jul;11(6):465-70. doi: 10.1097/00001813-200007000-00007.


Irinotecan (CPT-11) is a topoisomerase I inhibitor commonly used in the treatment of colorectal tumors. It is a prodrug, converted to an active metabolite, SN-38, by carboxylesterases (CEs). CEs are ubiquitary enzymes that react with numerous substrates. A specific CPT-11 converting enzyme was isolated from rat serum, with different kinetic properties than other CEs. We determined kinetic properties of specific CPT-11 CE activity (CPT-CE) in human normal liver and colon tumors. Km were very similar (3.4 microM in liver and 3.8 microM in colon tumors), but Vmax was higher in liver (2.7 pmol/min/mg protein) than in colon tumor (1.7 pmol/min/mg protein). CPT-CE and total CE (using p-nitro-phenylacetate as substrate) were weakly correlated in colon tumors. The large interpatient variability observed in liver CPT-CE activity could play a potential role in the pharmacokinetic variability observed with irinotecan.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Antineoplastic Agents, Phytogenic / pharmacology
  • Camptothecin / analogs & derivatives*
  • Camptothecin / pharmacology
  • Carboxylic Ester Hydrolases / metabolism*
  • Colon / drug effects
  • Colon / enzymology*
  • Colonic Neoplasms / enzymology*
  • Colonic Neoplasms / pathology
  • Colonic Neoplasms / surgery
  • DNA Topoisomerases, Type I / metabolism
  • Enzyme Activation / drug effects
  • Enzyme Inhibitors / pharmacology
  • Humans
  • Irinotecan
  • Kinetics
  • Liver / drug effects
  • Liver / enzymology*
  • Nitrophenols / metabolism*
  • Rats
  • Substrate Specificity
  • Topoisomerase I Inhibitors*


  • Antineoplastic Agents, Phytogenic
  • Enzyme Inhibitors
  • Nitrophenols
  • Topoisomerase I Inhibitors
  • Irinotecan
  • 4-nitrophenyl acetate
  • CPT-11 converting enzyme
  • Carboxylic Ester Hydrolases
  • DNA Topoisomerases, Type I
  • Camptothecin