title: Influence of ocular volume and lens status on pharmacokinetics and duration of action of intravitreal vascular endothelial growth factor inhibitors.
abstract: OBJECTIVE
  To assess the effects of ocular axial length, refraction, and lens status on pharmacokinetics and duration of action of the vascular endothelial growth factor (VEGF) inhibitors ranibizumab and bevacizumab after intravitreal injection in humans.
  
  
  METHODS
  In 119 eyes of 119 patients, aqueous humor was sampled at different time points after intravitreal injection of ranibizumab or bevacizumab, and either drug or VEGF concentrations were measured by enzyme-linked immunosorbent assays and Luminex multiplex bead technology, respectively. Relative deviation of the measured drug concentrations from the time-corrected mean values was calculated (n = 41). Repetitive VEGF measurements were preformed to identify the duration of complete suppression of ocular VEGF activity for individual eyes (n = 78). In addition, axial length, spherical equivalent refraction, and lens status were determined.
  
  
  RESULTS
  For neither ranibizumab nor bevacizumab, a correlation between ocular pharmacokinetics (as measured by relative deviation of drug concentration from the mean) and axial length was detected in phakic eyes (Spearman's correlation coefficient, r = 0.084; P = 0.600). Similarly, the duration of action of intravitreal ranibizumab (as measured by VEGF suppression time) did not correlate with spherical equivalent refraction in phakic eyes (Spearman's correlation coefficient, r = 0.164; P = 0.301) and was not different between phakic and pseudophakic eyes (P = 0.694; Mann-Whitney U test).
  
  
  CONCLUSIONS
  The results indicate that ocular volume and lens status have no relevant impact on ocular pharmacokinetics and duration of action of VEGF-inhibitory drugs and may, thus, be excluded as factors accounting for the high interindividual variability in morphologic and functional responses to intravitreal anti-VEGF therapy.
authors: *Department of Ophthalmology, University of Bonn, Bonn, Germany; †Department of Ophthalmology, University of Cologne, Cologne, Germany; and ‡Department of Ophthalmology, Pallas Clinics, Aarau, Switzerland.
authors: Tim U
authors: TU
authors: Krohne
authors: Philipp S
authors: PS
authors: Muether
authors: Nina K
authors: NK
authors: Stratmann
authors: Frank G
authors: FG
authors: Holz
authors: Bernd
authors: B
authors: Kirchhof
authors: Carsten H
authors: CH
authors: Meyer
authors: Sascha
authors: S
authors: Fauser
mesh_terms: D020533:Angiogenesis Inhibitors / Q000493:pharmacokinetics*; D061067:Antibodies, Monoclonal, Humanized / Q000493:pharmacokinetics*; D001082:Aqueous Humor / Q000378:metabolism*; D058452:Axial Length, Eye / Q000033:anatomy & histology*; D000068258:Bevacizumab; D001682:Biological Availability; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D058449:Intravitreal Injections; D007908:Lens, Crystalline / Q000502:physiology*; D008269:Macular Edema / Q000188:drug therapy / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D000069579:Ranibizumab; D012029:Refraction, Ocular / Q000502:physiology; D012164:Retinal Diseases / Q000188:drug therapy / Q000378:metabolism*; D012170:Retinal Vein Occlusion / Q000188:drug therapy / Q000378:metabolism; D013997:Time Factors; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors / Q000378:metabolism; D057135:Wet Macular Degeneration / Q000188:drug therapy / Q000378:metabolism
chemical_list: D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D000068258:Bevacizumab; D000069579:Ranibizumab