title: Assessment of Pharmacokinetic Interaction Between Capecitabine and Cetuximab in Metastatic Colorectal Cancer Patients.
abstract: This study focuses on the plasma disposition and metabolic activation of capecitabine (CCB) when administered alone or when combined with cetuximab (CTX).
  
  
  
  Twenty-four chemo-naïve patients with KRAS wild-type colorectal cancer were randomized into two arms and received either CCB alone (1,000 mg/m(2) bid p.o.), followed by CCB plus CTX (loading dose (LD)=400 mg/m(2) followed by 250 mg/m(2) weekly i.v. maintenance dose) (Arm A; n=12 patients (patients)) or CCB plus CTX followed by CCB alone (Arm B; n=12 patients). Plasma samples were collected from the cubital vein and CCB, 5'-desoxy-5-fluorocytidine (5'-DFCR) and 5'-desoxy-5 fluorouridine (5'-DFUR) were quantified by a sensitive, selective reversed phase high-performance liquid chromatography (HPLC) assay. Non-compartment pharmacokinetic parameters have been calculated by Phoenix WinNonlin.
  
  
  
  No clinically relevant impact of CTX on CCB pharmacokinetic parameters and metabolic conversion could be detected in both arms after statistical evaluation (ANOVA).
  
  
  
  From the pharmacokinetic point of view, co-administration of CTX to CCB seems to be safe.
authors.affiliation: Division of Clinical Pharmacy and Diagnostics, Centre of Pharmacy, University of Vienna, Vienna, Austria veronika.schreiber@univie.ac.at.
authors.forename: Veronika
authors.initials: V
authors.lastname: Rachar
authors.affiliation: Division of Clinical Pharmacy and Diagnostics, Centre of Pharmacy, University of Vienna, Vienna, Austria.
authors.forename: Martin
authors.initials: M
authors.lastname: Czejka
authors.affiliation: Division of Clinical Pharmacy and Diagnostics, Centre of Pharmacy, University of Vienna, Vienna, Austria.
authors.forename: Marie
authors.initials: M
authors.lastname: Kitzmueller
authors.affiliation: Division of Clinical Pharmacy and Diagnostics, Centre of Pharmacy, University of Vienna, Vienna, Austria.
authors.forename: Philipp
authors.initials: P
authors.lastname: Buchner
authors.affiliation: Ludwig Boltzmann Institute for Applied Cancer Research (LBI-ACR VIEnna)-LB-CTO and Applied Cancer Research-Institution for Translational Research Vienna (ACR-ITR VIEnna), Kaiser Franz Josef-Spital, 3rd Medical Department, Center for Oncology and Hematology, Vienna, Austria.
authors.forename: Maria
authors.initials: M
authors.lastname: Lichtneckert
authors.affiliation: 3rd Medical Department, Paracelsus Medical University Salzburg, Salzburg, Austria.
authors.forename: Richard
authors.initials: R
authors.lastname: Greil
authors.affiliation: Merck Austria GmbH, Vienna, Austria.
authors.forename: Herbert
authors.initials: H
authors.lastname: Geiler
authors.affiliation: Ludwig Boltzmann Institute for Applied Cancer Research (LBI-ACR VIEnna)-LB-CTO and Applied Cancer Research-Institution for Translational Research Vienna (ACR-ITR VIEnna), Kaiser Franz Josef-Spital, 3rd Medical Department, Center for Oncology and Hematology, Vienna, Austria.
authors.forename: Christian
authors.initials: C
authors.lastname: Dittrich
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D000069287:Capecitabine / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics; D000068818:Cetuximab / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood; D015179:Colorectal Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D004347:Drug Interactions; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics
chemical_list: C117307:KRAS protein, human; D000069287:Capecitabine; D016283:Proto-Oncogene Proteins p21(ras); D000068818:Cetuximab
keywords: Pharmacokinetic study; capecitabine; cetuximab; colorectal cancer; drug-drug interactions