title: Pharmacokinetics of bevacizumab after topical, subconjunctival, and intravitreal administration in rabbits.
abstract: OBJECTIVE
  To investigate the pharmacokinetics of bevacizumab in rabbits for three different routes of administrations: intravitreal injection, subconjunctival injection, and eye drops.
  
  
  METHODS
  Pigmented rabbits received bevacizumab in one eye by topical eye drops (1.25 mg/0.05 mL six times daily for the first 7 days), single subconjunctival injection (1.25 mg/0.05 mL), or single intravitreal injection (1.25 mg/0.05 mL). Bevacizumab concentrations in plasma and ocular tissues in the treated and fellow eyes were determined by sandwich enzyme-linked immunosorbent assay at 1, 2, 4, and 12 weeks after administration.
  
  
  RESULTS
  After intravitreal injection in the treated eye, the mean maximum concentrations (C(max)) of bevacizumab in the iris/ciliary body and retina/choroid were 109,192.6, and 93,990.0 ng/g, respectively, whereas after subconjunctival injection, the C(max) was 1418.7 and 295.8 ng/g, respectively. In the fellow eyes, when the drug was administered by intravitreal injection, the C(max) was 753.6 ng/g in the iris/ciliary body and 224.2 ng/g in the retina/choroid and by subconjunctival injection was 1192.9 and 187.0 ng/g, respectively. With eye drops, only a small level of bevacizumab was detected in the iris/ciliary body and retina/choroid. Systemic exposure to bevacizumab was at the same level when administered by intravitreal or subconjunctival injection.
  
  
  CONCLUSIONS
  Intravitreal injection of bevacizumab was the most effective route of administration for intraocular tissue. Also, bevacizumab injected subconjunctivally was transported into the intraocular tissues of the treated eyes at an effective level. Both intravitreal and subconjunctival injections of bevacizumab resulted in high plasma concentrations. Bevacizumab was distributed into the intraocular tissues in fellow eyes via the systemic circulation. This treatment may be effective for blocking vascular endothelial growth factor activity.
authors.affiliation: Department of Ophthalmology, Kagawa University Faculty of Medicine, Kagawa, Japan. nomoto@med.kagawa-u.ac.jp
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Nomoto
authors.forename: Fumio
authors.initials: F
authors.lastname: Shiraga
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Kuno
authors.forename: Erika
authors.initials: E
authors.lastname: Kimura
authors.forename: Shinobu
authors.initials: S
authors.lastname: Fujii
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Shinomiya
authors.forename: Alex K
authors.initials: AK
authors.lastname: Nugent
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Hirooka
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Baba