title: Effect of retinal permeability, diffusivity, and aqueous humor hydrodynamics on pharmacokinetics of drugs in the eye.
abstract: OBJECTIVE
  Retinal permeability is one of the important parameters that determine drug distribution during diseased retinal conditions, whose effect is still unclear. Thus, the main aim of this study was to understand the influence of varying retinal permeability (P) on drug distribution under normal (F1) and elevated vitreous outflow pathophysiologic conditions (F10) for a wide variety of drug diffusivities-high: D(-5) and low: D(-7).
  
  
  METHODS
  A computational model of the rabbit eye was developed that took into account the varying effects of convection during normal and pathophysiologic conditions.
  
  
  RESULTS
  High retinal permeability, P(-5), is associated with low peak macular concentration and a rapid clearance from the ocular chambers, with the retina as the major route of elimination. For low permeability, P(-7), there is very high peak macular concentration, slow elimination, and a buildup of drug concentration, which depends on vitreous outflow. The variation of t(1/2) with P was found to be of linear and nonlinear trends for F1 and F10 flow cases, respectively. Moreover, for D(-5) diffusivity, there was a 1.5-fold increase and a 1.6-fold decrease in t(1/2) values when the retinal permeability values were P(-5) and P(-7). On the contrary, for D(-7) diffusivity, there was a 2.5-fold decrease and a 1.4-fold increase in t(1/2) values for P(-5) and P(-7), with t(1/2) increasing for P(-6) during both high and low diffusivities.
  
  
  CONCLUSIONS
  Thus, the combined effect of variables P, D, and F are important factors that should be considered in order to determine drug dosage. This study could be used to estimate the drug distribution and elimination for (1) wide range of physicochemical properties of drugs and (2) normal and abnormally elevated vitreous flows during the diseased condition of the eye. These results could help in obtaining essential information about the treatment protocol for targeted retinal diseases while simultaneously avoiding the toxic effects of these drugs.
authors.affiliation: Department of Mechanical Engineering, University of Cincinnati, Cincinnati, OH 45221-0072, USA.
authors.forename: Mahesh K
authors.initials: MK
authors.lastname: Krishnamoorthy
authors.forename: Juyoung
authors.initials: J
authors.lastname: Park
authors.forename: James J
authors.initials: JJ
authors.lastname: Augsburger
authors.forename: Rupak K
authors.initials: RK
authors.lastname: Banerjee
mesh_terms: D000465:Algorithms; D000818:Animals; D001082:Aqueous Humor / Q000737:chemistry* / Q000502:physiology*; D001813:Blood-Retinal Barrier / Q000502:physiology; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D003198:Computer Simulation; D018481:Convection; D004058:Diffusion; D006207:Half-Life; D008953:Models, Anatomic; D015233:Models, Statistical; D010539:Permeability; D004364:Pharmaceutical Preparations / Q000737:chemistry* / Q000378:metabolism*; D010599:Pharmacokinetics; D011817:Rabbits; D012160:Retina / Q000737:chemistry* / Q000378:metabolism*; D014822:Vitreous Body / Q000737:chemistry / Q000502:physiology
chemical_list: D004364:Pharmaceutical Preparations