title: Effect of vitrectomy on aqueous VEGF concentration and pharmacokinetics of bevacizumab in macaque monkeys.
abstract: OBJECTIVE
  To evaluate the effect of vitrectomy on the concentration of vascular endothelial growth factor (VEGF) and the pharmacokinetics of intravitreally injected bevacizumab in the aqueous humor in cynomolgus macaques.
  
  
  METHODS
  Pars plana lensectomy and a standard three-port vitrectomy were performed in one eye each of six macaques. After a minimal 12-week healing period, the vitrectomized eyes received an intravitreal injection of bevacizumab (1.25 mg/50 μL). Aqueous humor and venous blood samples were obtained from the macaques just before vitrectomy, just before injection of bevacizumab, on days 1, 3, and 7, and during weeks 2, 4, 6, and 8 after the injection. The bevacizumab and VEGF concentrations were measured by using enzyme-linked immunosorbent assay.
  
  
  RESULTS
  The VEGF concentrations in the aqueous humor ranged from 52.6 to 113.9 pg/mL (mean ± standard deviation [SD], 81.7 ± 27.0 pg/mL) before vitrectomy and 20.7 to 72.7 pg/mL (mean ± SD, 51.4 ± 20.5 pg/mL) 3 months after vitrectomy, a difference that reached significance (P = 0.03). The aqueous VEGF concentrations decreased to less than 9.0 pg/mL, the lower limit of detection, in all eyes between 1 and 7 days after injection of bevacizumab. The mean half-life of 1.25 mg intravitreally injected bevacizumab was 1.5 ± 0.6 days (range, 1.0-2.4 days) in the aqueous humor.
  
  
  CONCLUSIONS
  The VEGF concentration in the aqueous humor decreased and the half-life of the intravitreally injected bevacizumab was shorter in vitrectomized eyes.
authors: Department of Ophthalmology, Shiga University of Medical Science, Otsu, Japan. kakinoki@belle.shiga-med.ac.jp
authors: Masashi
authors: M
authors: Kakinoki
authors: Osamu
authors: O
authors: Sawada
authors: Tomoko
authors: T
authors: Sawada
authors: Yoshitsugu
authors: Y
authors: Saishin
authors: Hajime
authors: H
authors: Kawamura
authors: Masahito
authors: M
authors: Ohji
mesh_terms: D020533:Angiogenesis Inhibitors / Q000493:pharmacokinetics*; D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000493:pharmacokinetics*; D001082:Aqueous Humor / Q000378:metabolism*; D000068258:Bevacizumab; D004797:Enzyme-Linked Immunosorbent Assay; D006207:Half-Life; D058449:Intravitreal Injections; D008252:Macaca fascicularis; D008297:Male; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*; D014821:Vitrectomy
chemical_list: D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; D042461:Vascular Endothelial Growth Factor A; D000068258:Bevacizumab