title: Clinical pharmacokinetics of capecitabine and its metabolites in combination with the monoclonal antibody bevacizumab.
abstract: OBJECTIVE
  Capecitabine, designed as a pro-drug to the cytotoxic agent 5-fluorouracil, is widely used in the management of colorectal cancer. This study was designed to investigate whether co-administration of the monoclonal antibody bevacizumab (BVZ) shows potential to modulate the plasma disposition of capecitabine (CCB) and its metabolites.
  
  
  METHODS
  Nine patients treated with CCB and BVZ for advanced colorectal cancer entered this pharmacokinetic study. In the first cycle CCB was given alone at doses of 1,250 mg/m2 bi-daily for two weeks with one week rest. In the second cycle BVZ co-administration started simultaneously with oral intake of CCB by short infusion of 7.5 mg/kg.
  
  
  RESULTS
  Mean plasma concentration time curves of CCB and its metabolites were insignificantly lower in the BVZ combination regimen compared to CCB monotherapy. After repeated cycles of BVZ no significant pharmacokinetic interaction was observed.
  
  
  CONCLUSIONS
  From the pharmacokinetic point of view and in agreement with numerous clinical study data, co-administration of BVZ with CCB appears to be safe and efficient.
authors: Division of Clinical Pharmacy and Diagnostics, Faculty of Life Sciences, University of Vienna, Vienna, Austria Austrian Society of Applied Pharmacokinetics, Vienna, Austria andre.farkouh@univie.ac.at.
authors: Andre
authors: A
authors: Farkouh
authors: Department of Oncology, University Clinic of Internal Medicine I, Medical University Vienna, General Hospital Vienna, Vienna, Austria Austrian Society of Applied Pharmacokinetics, Vienna, Austria.
authors: Werner
authors: W
authors: Scheithauer
authors: Division of Clinical Pharmacy and Diagnostics, Faculty of Life Sciences, University of Vienna, Vienna, Austria Austrian Society of Applied Pharmacokinetics, Vienna, Austria.
authors: Philipp
authors: P
authors: Buchner
authors: Department of Internal Medicine, University Clinic of Internal Medicine I, Medical University Vienna, General Hospital Vienna, Vienna, Austria Austrian Society of Applied Pharmacokinetics, Vienna, Austria.
authors: Apostolos
authors: A
authors: Georgopoulos
authors: Department of Internal Medicine and Oncology, Hospital Rudolfstiftung, Vienna, Austria.
authors: Johannes
authors: J
authors: Schueller
authors: Department of Internal Medicine, St. John of God Hospital Vienna, Vienna, Austria.
authors: Birgit
authors: B
authors: Gruenberger
authors: Division of Clinical Pharmacy and Diagnostics, Faculty of Life Sciences, University of Vienna, Vienna, Austria Austrian Society of Applied Pharmacokinetics, Vienna, Austria.
authors: Martin
authors: M
authors: Czejka
mesh_terms: D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000494:pharmacology*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000493:pharmacokinetics* / Q000494:pharmacology; D000068258:Bevacizumab; D000069287:Capecitabine; D015179:Colorectal Neoplasms / Q000097:blood / Q000188:drug therapy / Q000378:metabolism*; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics; D005260:Female; D005467:Floxuridine / Q000097:blood; D005472:Fluorouracil / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics; D006801:Humans; D008297:Male; D008875:Middle Aged
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D005467:Floxuridine; D003841:Deoxycytidine; D000068258:Bevacizumab; D000069287:Capecitabine; C418208:5'-deoxy-5-fluorocytidine; D005472:Fluorouracil; C025034:doxifluridine
keywords: Capecitabine; bevacizumab; colorectal cancer; drug-drug interaction; pharmacokinetics