title: In vivo disposition of irinotecan (CPT-11) and its metabolites in combination with the monoclonal antibody cetuximab.
abstract: BACKGROUND
  The present study was designed to investigate whether a combination of irinotecan and the monoclonal antibody cetuximab shows potential to modulate the pharmacokinetics of irinotecan and its metabolites.
  
  
  METHODS
  All patients, suffering from advanced colorectal cancer, received irinotecan (350 mg/m2) every third week and cetuximab as a loading dose (400 mg/m2) on day 2, followed by a weekly maintenance dose (250 mg/m2). Plasma samples were analysed after the first (MONO) and second (CMAB) irinotecan infusions.
  
  
  RESULTS
  No significant alterations in the plasma concentrations and pharmacokinetics of irinotecan and its metabolites were observed after combination with cetuximab. Only differentiation of irinotecan into lactone and carboxylate plasma concentrations resulted in a distinctly lower cmax of the active lactone in the CMAB and a significantly higherAUClast in the MONO schedule (p<0.02).
  
  
  CONCLUSIONS
  The results of this study indicated that cetuximab has no clinically relevant impact on the pharmacokinetics of irinotecan, its activation into SN-38, or its detoxification by beta-D-glucuronidation.
authors.affiliation: Department of Clinical Pharmacy and Diagnostics, Faculty of Life Sciences, University of Vienna, Althanstrasse 14, A-1090 Vienna. dagmar.ettlinger@meduniwien.ac.at
authors.forename: Dagmar E
authors.initials: DE
authors.lastname: Ettlinger
authors.forename: Markus
authors.initials: M
authors.lastname: Mitterhauser
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Wadsak
authors.forename: Eva
authors.initials: E
authors.lastname: Ostermann
authors.forename: André
authors.initials: A
authors.lastname: Farkouh
authors.forename: Johann
authors.initials: J
authors.lastname: Schueller
authors.forename: Martin
authors.initials: M
authors.lastname: Czejka
mesh_terms: D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000494:pharmacology*; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000493:pharmacokinetics / Q000494:pharmacology*; D001711:Biotransformation; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics; D000068818:Cetuximab; D015179:Colorectal Neoplasms / Q000097:blood / Q000188:drug therapy / Q000378:metabolism*; D018592:Cross-Over Studies; D004347:Drug Interactions; D005260:Female; D020719:Glucuronides / Q000097:blood; D006801:Humans; D000077146:Irinotecan; D008297:Male; D008875:Middle Aged; D011355:Prodrugs / Q000008:administration & dosage / Q000493:pharmacokinetics*; D011446:Prospective Studies
chemical_list: C441475:7-ethyl-10-hydroxycamptothecin glucuronide; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D020719:Glucuronides; D011355:Prodrugs; D000077146:Irinotecan; D000068818:Cetuximab; D002166:Camptothecin