title: An enzyme-linked immunosorbent assay to study bevacizumab pharmacokinetics.
abstract: BACKGROUND
  Bevacizumab is an antivascular endothelial growth factor humanized monoclonal antibody used to inhibit angiogenesis in cancer. It displays an important interindividual pharmacokinetic variability, which could explain part of the interindividual differences in clinical response. Therefore, an assay to measure bevacizumab serum concentrations is needed.
  
  
  METHODS
  An enzyme-linked immunosorbent assay was developed using microtiter plates sensitised with vascular endothelial growth factor 165, a recombinant form of vascular endothelial growth factor. Lower and upper limits of quantitation as well as limit of detection were determined. Eight calibrators and three quality controls, with concentrations of 5 mg/L, 30 mg/L, and 75 mg/L, were tested on five occasions initially and on five subsequent occasions. Trough and peak serum concentrations of bevacizumab were measured in patients with metastatic colorectal cancer. Bevacizumab concentrations were described using a two-compartment population pharmacokinetic model with first-order constants.
  
  
  RESULTS
  Imprecision and accuracy of calibrators and quality controls were 20% or less, except for the zero calibrator. The limit of detection was 0.033 mg/L. Lower and upper limits of quantitation were 5 and 75 mg/L, respectively. A total of 175 blood samples was available for analysis from 16 patients. Median (range) trough and peak concentrations during the treatment were 47.2 (9.6-106.9) mg/L and 159.3 (33.0-327.3) mg/L, respectively.
  
  
  CONCLUSIONS
  This method is rapid, accurate, reproducible, and may be useful for pharmacokinetic and pharmacokinetic-pharmacodynamic studies as well as in therapeutic drug monitoring of bevacizumab.
authors: Université François Rabelais de Tours, Genetics, Immunotherapy, Chemistry and Cancer, Tours, France. david.ternant@free.fr
authors: David
authors: D
authors: Ternant
authors: Nicolas
authors: N
authors: Cézé
authors: Thierry
authors: T
authors: Lecomte
authors: Danielle
authors: D
authors: Degenne
authors: Anne-Claire
authors: AC
authors: Duveau
authors: Hervé
authors: H
authors: Watier
authors: Etienne
authors: E
authors: Dorval
authors: Gilles
authors: G
authors: Paintaud
mesh_terms: D020533:Angiogenesis Inhibitors / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D000911:Antibodies, Monoclonal / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D019540:Area Under Curve; D000068258:Bevacizumab; D015179:Colorectal Neoplasms / Q000097:blood / Q000188:drug therapy; D016903:Drug Monitoring; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D006801:Humans
chemical_list: D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab