In Vivo Disposition of Irinotecan (CPT-11) and its Metabolites in Combination with the Monoclonal Antibody Cetuximab

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. Patients and Methods: All patients, suffering from advanced colorectal cancer, recei...

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Bibliographic Details
Published in:Anticancer research 2006-03, Vol.26 (2B), p.1337-1341
Main Authors: ETTLINGER, Dagmar E, MITTERHAUSER, Markus, WADSAK, Wolfgang, OSTERMANN, Eva, FARKOUH, André, SCHUELLER, Johann, CZEJKA, Martin
Format: Article
Language:English
Subjects:
Aged
Antibodies, Monoclonal - administration & dosage
Antibodies, Monoclonal - pharmacology
Antibodies, Monoclonal, Humanized
Antineoplastic Combined Chemotherapy Protocols - pharmacokinetics
Antineoplastic Combined Chemotherapy Protocols - pharmacology
Biological and medical sciences
Biotransformation
Camptothecin - administration & dosage
Camptothecin - analogs & derivatives
Camptothecin - blood
Camptothecin - pharmacokinetics
Cetuximab
Colorectal Neoplasms - blood
Colorectal Neoplasms - drug therapy
Colorectal Neoplasms - metabolism
Cross-Over Studies
Drug Interactions
Female
Gastroenterology. Liver. Pancreas. Abdomen
Glucuronides - blood
Humans
Male
Medical sciences
Middle Aged
Prodrugs - administration & dosage
Prodrugs - pharmacokinetics
Prospective Studies
Stomach. Duodenum. Small intestine. Colon. Rectum. Anus
Tumors
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Summary: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. Patients and Methods: All patients, suffering from advanced colorectal cancer, received irinotecan (350 mg/m 2 ) every third week and cetuximab as a loading dose (400 mg/m 2 ) on day 2, followed by a weekly maintenance dose (250 mg/m 2 ). 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 c max of the active lactone in the CMAB and a significantly higher AUC last in the MONO schedule (p
ISSN:0250-7005
1791-7530