title: Serum concentrations of bevacizumab (avastin) and vascular endothelial growth factor in infants with retinopathy of prematurity.
abstract: OBJECTIVE
  To determine the serum concentrations of bevacizumab and vascular endothelial growth factor (VEGF) in infants with retinopathy of prematurity (ROP) who received intravitreal bevacizumab; and to determine whether the changes in the serum concentration of bevacizumab were significantly correlated with the serum concentration of VEGF after intravitreal bevacizumab.
  
  
  METHODS
  Case series.
  
  
  METHODS
  Eleven infants (4 girls and 7 boys) with ROP were studied. They received 0.25 mg or 0.5 mg of intravitreal bevacizumab to either 1 eye (unilateral cases) or both eyes (bilateral cases) with vascularly active ROP. Serum samples were collected before and 1 day, 1 week, and 2 weeks after the intravitreal bevacizumab. The serum concentrations of bevacizumab and VEGF were measured by enzyme-linked immunosorbent assay, and the correlation in the serum levels between the 2 was determined.
  
  
  RESULTS
  The serum concentration of bevacizumab before and 1 day, 1week, and 2 weeks after a total of 0.5 mg of intravitreal bevacizumab was 0 ng/mL, 195 ± 324 ng/mL, 946 ± 680 ng/mL, and 1214 ± 351 ng/mL, respectively. The serum bevacizumab level before and 1 day and 1 week after a total 1.0 mg of intravitreal bevacizumab was 0 ng/mL, 248 ± 174 ng/mL, and 548 ± 89 ng/mL, respectively. The serum concentration of VEGF before and 1 day, 1 week, and 2 weeks after a total of 0.5 mg intravitreal bevacizumab was 1628 ± 929 pg/mL, 427 ± 140 pg/mL, 246 ± 110 pg/mL, and 269 ± 157 pg/mL, respectively. There was a significant negative correlation (r = -0.575, P = .0125) between the serum concentration of bevacizumab and VEGF when a total of 0.25 mg or 0.5 mg of bevacizumab was injected.
  
  
  CONCLUSIONS
  These results indicate that bevacizumab can escape from the eye into the systemic circulation and reduce the serum level of VEGF in infants with ROP. Continued extensive evaluations of infants are warranted for possible effects after intravitreal bevacizumab in ROP patients.
authors.affiliation: Department of Applied Visual Science, Osaka University Graduate School of Medicine, Suita, Japan.
authors.forename: Tatsuhiko
authors.initials: T
authors.lastname: Sato
authors.forename: Kazuko
authors.initials: K
authors.lastname: Wada
authors.forename: Hitomi
authors.initials: H
authors.lastname: Arahori
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Kuno
authors.forename: Kenji
authors.initials: K
authors.lastname: Imoto
authors.forename: Chiharu
authors.initials: C
authors.lastname: Iwahashi-Shima
authors.forename: Shunji
authors.initials: S
authors.lastname: Kusaka
mesh_terms: D020533:Angiogenesis Inhibitors / Q000493:pharmacokinetics*; D061067:Antibodies, Monoclonal, Humanized / Q000493:pharmacokinetics*; D000068258:Bevacizumab; D001682:Biological Availability; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005865:Gestational Age; D006801:Humans; D052577:Infant, Extremely Low Birth Weight; D007231:Infant, Newborn; D058449:Intravitreal Injections; D017075:Laser Coagulation; D008297:Male; D012178:Retinopathy of Prematurity / Q000378:metabolism* / Q000601:surgery; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors / Q000097:blood*
chemical_list: D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D000068258:Bevacizumab