title: Pharmacokinetics of bevacizumab after topical and intravitreal administration in human eyes.
abstract: BACKGROUND
  Topical bevacizumab is a potential treatment modality for corneal neovascularization, and several recent studies have demonstrated its efficacy. No previous study of the pharmacokinetics of topical bevacizumab has been performed in human eyes. The purpose of this study is to investigate the pharmacokinetics of topical administration of bevacizumab in human eyes, and also to compare the pharmacokinetics of intravitreal bevacizumab injections with previously reported data.
  
  
  METHODS
  Twenty-two (22 eyes) were included in this study, and divided into four groups: eight patients received topical bevacizumab and aqueous samples were obtained 1 hour later during cataract extraction surgery (group 1), eight patients received topical bevacizumab and vitreous samples were obtained 1 day later during pars-plana vitrectomy (PPV) (group 2), three patients received intravitreal bevacizumab and vitreous samples were obtained during PPV (group 3). Vitreous samples from three patients who received no bevacizumab served as controls (group 4). All samples underwent enzyme-linked immunosorbent assay to detect bevacizumab.
  
  
  RESULTS
  No bevacizumab was detected in the aqueous or vitreous of any topically treated eyes. The mean vitreal half-life for intravitreally injected bevacizumab was 4.9 days in four non-vitrectomized eyes and 0.66 days in one previously vitrectomized eye.
  
  
  CONCLUSIONS
  Topically administered bevacizumab does not penetrate the cornea into the anterior chamber and vitreous cavity, indicating that topical use for treating corneal neovascularization has minimal risk of intraocular penetration and adverse events related to intraocular vascular endothelial growth factor inhibition. The half-life following intravitreal bevacizumab injection measured in this study is comparable to that of previous reports, and includes the first demonstration of a significantly reduced half-life following intravitreal injection in a previously vitrectomized eye.
authors.affiliation: Department of Ophthalmology, Tel-Aviv Sourasky Medical Center, Affiliated to the Sackler School of Medicine, Tel Aviv University, Tel Aviv, 6 Weizman Street, Tel-Aviv, 64239, Israel, elad_moi@netvision.net.il.
authors.forename: Elad
authors.initials: E
authors.lastname: Moisseiev
authors.forename: Michael
authors.initials: M
authors.lastname: Waisbourd
authors.forename: Elad
authors.initials: E
authors.lastname: Ben-Artsi
authors.forename: Eliya
authors.initials: E
authors.lastname: Levinger
authors.forename: Adiel
authors.initials: A
authors.lastname: Barak
authors.forename: Tad
authors.initials: T
authors.lastname: Daniels
authors.forename: Karl
authors.initials: K
authors.lastname: Csaky
authors.forename: Anat
authors.initials: A
authors.lastname: Loewenstein
authors.forename: Irina S
authors.initials: IS
authors.lastname: Barequet
mesh_terms: D000287:Administration, Topical; D000368:Aged; D000369:Aged, 80 and over; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics*; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001082:Aqueous Humor / Q000378:metabolism*; D000068258:Bevacizumab; D002387:Cataract Extraction; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006207:Half-Life; D006801:Humans; D058449:Intravitreal Injections; D008297:Male; D008875:Middle Aged; D014018:Tissue Distribution; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors; D014822:Vitreous Body / Q000378:metabolism*
chemical_list: D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D000068258:Bevacizumab