title: Intraocular pharmacokinetics after a single intravitreal injection of 1.5 mg versus 3.0 mg of bevacizumab in humans.
abstract: OBJECTIVE
  To compare the concentration of unbound bevacizumab in the anterior chamber of patients with macular edema, who received a single intravitreal injection of two different dosages.
  
  
  METHODS
  This was a comparative, interventional case series. Twenty-nine nonvitrectomized eyes of 29 patients with significant lens opacities and concurrent macular edema were included in the study. All patients were treated by a single dose of intravitreal injection of bevacizumab 1.5 mg (Group A, n = 13) or 3.0 mg (Group B, n = 16). Subsequent phacoemulsification and aspiration of an aqueous humor samples were performed at various intervals (1-60 days). The axial length of the globe was measured using the IOLMaster to calculate the total volume and corresponding globe size-corrected half-time. The concentration of unbound bevacizumab was measured by enzyme-linked immunosorbent assay and pharmacokinetic parameters including half-time of elimination.
  
  
  RESULTS
  The mean peak concentration was observed in both groups on the first day after intravitreal bevacizumab injection. The mean concentration of unbound bevacizumab ranged in Group A from 17.5 μg/mL at baseline to 0.66 μg/mL at Day 57 and in Group B from 28.3 μg/mL at baseline to 0.00 μg/mL at 54 days. The axial lengths of all injected eyes were not significantly different between Group A (mean values, 23.026 mm, SD 1.21) and Group B (mean, 23.313 mm, SD 1.00; P = 0.31). Regression analysis determined elimination half-time values of 7.85 days (R2 = 0.75) in Group A and 11.67 days (R2 = 0.91) in Group B. Similar half-times were calculated for globe size-corrected concentrations with 8.21 days (R2 = 0.81) in Group A and 11.17 days (R2 = 0.88) in Group B.
  
  
  CONCLUSIONS
  Single- and double-dose injections have similar pharmacokinetic characteristics in a first-order exponential decay function. The globe size-corrected concentration and half-time did not affect the calculated half-time in both groups. Doubled dosing induced a higher peak concentration at baseline, but the presumed extended biologic active concentration was no longer statistically significant after 6 weeks. The application of twice the dosage does not double the duration of its efficacy; it rather appears to extend the pharmacological duration by 1 half-time or approximately 8 days to 11 days.
authors: Department of Ophthalmology, University of Bonn, Germany. meyer_eye@yahoo.com
authors: Carsten H
authors: CH
authors: Meyer
authors: Tim U
authors: TU
authors: Krohne
authors: Frank G
authors: FG
authors: Holz
mesh_terms: D020533:Angiogenesis Inhibitors / Q000493:pharmacokinetics*; D061067:Antibodies, Monoclonal, Humanized / Q000493:pharmacokinetics*; D001082:Aqueous Humor / Q000378:metabolism*; D000068258:Bevacizumab; D001682:Biological Availability; D002386:Cataract / Q000150:complications; D004797:Enzyme-Linked Immunosorbent Assay; D005451:Fluorescein Angiography; D006207:Half-Life; D006801:Humans; D058449:Intravitreal Injections; D008269:Macular Edema / Q000150:complications; D008875:Middle Aged; D018918:Phacoemulsification; D011446:Prospective Studies; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors
chemical_list: D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D000068258:Bevacizumab