An enzyme-linked immunosorbent assay to study bevacizumab pharmacokinetics.
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.
Ternant
David
D
Université François Rabelais de Tours, Genetics, Immunotherapy, Chemistry and Cancer, Tours, France. david.ternant@free.fr
Cézé
Nicolas
N
Lecomte
Thierry
T
Degenne
Danielle
D
Duveau
Anne-Claire
AC
Watier
Hervé
H
Dorval
Etienne
E
Paintaud
Gilles
G
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
D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab