title: Pharmacokinetics of intravitreal bevacizumab (Avastin).
abstract: OBJECTIVE
  To describe the pharmacokinetics of 1.25 mg of intravitreal bevacizumab (Avastin).
  
  
  METHODS
  Experimental animal study.
  
  
  METHODS
  Twenty Dutch-belted rabbits.
  
  
  METHODS
  One eye of each of 20 rabbits was injected with 1.25 mg of intravitreal bevacizumab. Both eyes of each of 4 rabbits were enucleated at days 1, 3, 8, 15, and 29. Bevacizumab concentrations were measured in aqueous fluid, whole vitreous, and serum.
  
  
  METHODS
  Bevacizumab concentrations in the aqueous, vitreous, and serum.
  
  
  RESULTS
  Whereas vitreous concentrations of bevacizumab declined in a monoexponential fashion with a half-life of 4.32 days, concentrations of >10 microg/ml bevacizumab were maintained in the vitreous humor for 30 days. Bevacizumab concentrations in the aqueous humor of the injected eye reached a peak concentration of 37.7 microg/ml 3 days after drug administration. A maximum serum concentration of 3.3 mug/ml was achieved 8 days after intravitreal injection and the concentration fell below 1 microg/ml 29 days after injection. Elimination of bevacizumab from the aqueous humor and serum paralleled that found in the vitreous humor, with half-life values of 4.88 days and 6.86 days, respectively. Very low concentrations of bevacizumab were detected in the fellow uninjected eye. Concentrations of bevacizumab in the vitreous of the fellow eye varied incrementally, from 0.35 ng/ml at 1 day to 11.17 ng/ml at 4 weeks. Concentrations of bevacizumab in the aqueous humor of the fellow eye reached their peak at 1 week, at 29.4 ng/ml, and declined to 4.56 ng/ml at 4 weeks.
  
  
  CONCLUSIONS
  The vitreous half-life of 1.25 mg intravitreal bevacizumab is 4.32 days in a rabbit eye. Very small amounts of bevacizumab were detected in the serum and in the fellow uninjected eye.
authors.affiliation: Department of Ophthalmology, Mayo Clinic, Rochester, Minnesota 55905, USA. sbakri@hotmail.com
authors.forename: Sophie J
authors.initials: SJ
authors.lastname: Bakri
authors.forename: Melissa R
authors.initials: MR
authors.lastname: Snyder
authors.forename: Joel M
authors.initials: JM
authors.lastname: Reid
authors.forename: Jose S
authors.initials: JS
authors.lastname: Pulido
authors.forename: Ravinder J
authors.initials: RJ
authors.lastname: Singh
mesh_terms: D020533:Angiogenesis Inhibitors / Q000493:pharmacokinetics*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics*; D061067:Antibodies, Monoclonal, Humanized; D001082:Aqueous Humor / Q000378:metabolism*; D000068258:Bevacizumab; D006207:Half-Life; D008297:Male; D011817:Rabbits; D014018:Tissue Distribution; D042461:Vascular Endothelial Growth Factor A / Q000276:immunology; D014822:Vitreous Body / Q000378:metabolism*
chemical_list: D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D000068258:Bevacizumab