title: Pharmacokinetics of pars plana intravitreal injections versus microcannula suprachoroidal injections of bevacizumab in a porcine model.
abstract: OBJECTIVE
  To compare the pharmacokinetics and tissue response between intravitreal and microcannulation injections into the suprachoroidal space using bevacizumab.
  
  
  METHODS
  Sixty-two pigs were studied. Either a pars plana intravitreal bevacizumab or a viscoelastic-enhanced microcannula suprachoroidal injection was performed with either 1.25 mg (group 1) or 3 mg (group 2). In group 1, six animals were euthanatized at 0.5, 7, 30, 60, 90, and 120 days after injection (n = 36). In group 2, six animals were euthanatized at 0.5, 7, 14, and 32 days (n = 24). Eyes were enucleated, dissected, and snap-frozen, or they were fixed for histology. Analysis of drug tissue levels was performed at two separate laboratories using masked specimens.
  
  
  RESULTS
  Both laboratories were confirmatory. Intravitreal bevacizumab pharmacokinetics demonstrated a gradual decline in tissue levels over 30 to 60 days in both groups 1 and 2. In addition, suprachoroidal bevacizumab tissue levels declined rapidly and were not measurable at or beyond 7 days. Vitreitis and granulomatous vasculitis were noted in 7 of 30 intravitreal injection eyes. Immunohistology suggested a distinctive drug distribution.
  
  
  CONCLUSIONS
  Direct intravitreal injection of bevacizumab has a more sustained pharmacologic profile than does a similar dose delivered to the suprachoroidal space. Intravitreal injections distributed more to the inner retina, whereas suprachoroidal delivery occurred primarily at the choroid, retinal pigment epithelium, and photoreceptor outer segments. Sustained release formulation of larger biological molecules should be considered to optimize suprachoroidal delivery. Inflammation from injections is granulomatous, seen only with intravitreal injections, and may result from either an altered immune response or a dose-related effect.
authors: Emory Eye Center, Department of Ophthalmology, Emory University, Atlanta, Georgia 30322, USA. tolsen@emory.edu
authors: Timothy W
authors: TW
authors: Olsen
authors: Xiao
authors: X
authors: Feng
authors: Kathy
authors: K
authors: Wabner
authors: Karl
authors: K
authors: Csaky
authors: Stefan
authors: S
authors: Pambuccian
authors: J Douglas
authors: JD
authors: Cameron
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000493:pharmacokinetics*; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab; D002404:Catheterization / Q000379:methods*; D002829:Choroid / Q000276:immunology / Q000378:metabolism*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D005500:Follow-Up Studies; D007111:Immunity, Cellular / Q000187:drug effects; D058449:Intravitreal Injections; D008268:Macular Degeneration / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D008904:Miniaturization; D055214:Retinal Photoreceptor Cell Outer Segment / Q000276:immunology / Q000378:metabolism*; D055213:Retinal Pigment Epithelium / Q000276:immunology / Q000378:metabolism*; D013552:Swine; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab