Pharmacokinetics of bevacizumab and its effects on serum VEGF and IGF-1 in infants with retinopathy of prematurity

Invest Ophthalmol Vis Sci. 2015 Jan 22;56(2):956-61. doi: 10.1167/iovs.14-15842.

Abstract

Purpose: To measure serum levels of bevacizumab and to compare serum levels of free vascular endothelial growth factor (VEGF) and insulin-like growth factor-1 (IGF-1) in infants who were treated with either intravitreal injection of bevacizumab (IVB) or laser for type 1 retinopathy of prematurity (ROP).

Methods: Twenty-four infants with type 1 ROP were randomized into three treatment groups: IVB at 0.625 mg per eye per dose, IVB at 0.25 mg per eye per dose, and laser. Blood samples were collected prior to treatment and on posttreatment days 2, 14, 42, and 60. Weekly body weights were documented from birth until 60 days post treatment. Serum levels of bevacizumab, free VEGF, and IGF-1 were measured with enzyme-linked immunosorbent assay (ELISA).

Results: Serum bevacizumab was detected 2 days after the injection, peaked at 14 days, and persisted for up to 60 days with half-life of 21 days. Area under the curve (AUC) analysis showed that systemic exposure to bevacizumab was variable among the subjects and was dose dependent. Serum free VEGF levels decreased in all three subgroups 2 days post treatment, with more significant reductions found in both IVB-treated groups, P = 0.0001. Serum IGF-1 levels were lower in both IVB-treated groups.

Conclusions: Clearance of bevacizumab from the bloodstream in premature infants takes at least 2 months. Although serum free VEGF levels decreased following either laser or bevacizumab treatment, the reductions were more significant in the IVB-treated groups. Potential long-term effects of systemic exposure to bevacizumab in infants need to be studied further.

Keywords: VEGF; bevacizumab; intraocular injection; laser; retinopathy of prematurity.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiogenesis Inhibitors / administration & dosage
  • Angiogenesis Inhibitors / pharmacokinetics
  • Antibodies, Monoclonal, Humanized / administration & dosage
  • Antibodies, Monoclonal, Humanized / pharmacokinetics*
  • Bevacizumab
  • Dose-Response Relationship, Drug
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Follow-Up Studies
  • Gestational Age
  • Humans
  • Infant
  • Infant, Newborn
  • Insulin-Like Growth Factor I / drug effects
  • Insulin-Like Growth Factor I / metabolism*
  • Intravitreal Injections
  • Male
  • Retinopathy of Prematurity / blood
  • Retinopathy of Prematurity / drug therapy*
  • Retrospective Studies
  • Treatment Outcome
  • Vascular Endothelial Growth Factor A / antagonists & inhibitors
  • Vascular Endothelial Growth Factor A / blood*

Substances

  • Angiogenesis Inhibitors
  • Antibodies, Monoclonal, Humanized
  • Vascular Endothelial Growth Factor A
  • Bevacizumab
  • Insulin-Like Growth Factor I