Retina-choroid-sclera permeability for ophthalmic drugs in the vitreous to blood direction: quantitative assessment.
OBJECTIVE
To determine the outward permeability of retina-choroid-sclera (RCS) layer for different ophthalmic drugs and to develop correlations between drug physicochemical properties and RCS permeability.


METHODS
A finite volume model was developed to simulate pharmacokinetics in the eye following drug administration by intravitreal injection. The RCS permeability was determined for 32 compounds by best fitting the drug concentration-time profile obtained by simulation with previously reported experimental data. Multiple linear regression was then used to develop correlations between best fit RCS permeability and drugs physicochemical properties.


RESULTS
The RCS drug permeabilities had values that ranged over 3 × 10(-6) m/s. Regression analysis for hydrophilic compounds showed that more than 92% of the variation in permeability values can be explained by correlative models of drug properties that include logarithm of the octanol-water partition coefficient (LogP), protein binding (PB), number of hydrogen bond acceptors (HBA), hydrogen bond donors (HBD), polar surface area (PSA) and dissociation constant (pKa) as independent variables. Regression analysis for lipophilic compounds showed that no significant correlation can be found between just physicochemical properties and RCS permeability.


CONCLUSIONS
Using the RCS permeability obtained from this study for different drugs, one can predict pharmacokinetics of intravitreal drug delivery systems such as solid implants or colloidal systems. Furthermore, the developed correlations between RCS permeability and physicochemical properties of drugs are useful in early drug development by predicting RCS permeability and drug concentration in the vitreous without experimental data.
Department of Chemical and Petroleum Engineering, Sharif University of Technology, Tehran, Iran.
Nahid
N
Haghjou
Mohammad J
MJ
Abdekhodaie
Yu-Ling
YL
Cheng
D000818:Animals; D002829:Choroid / Q000378:metabolism*; D003198:Computer Simulation; D058449:Intravitreal Injections; D016014:Linear Models; D008954:Models, Biological; D008958:Models, Molecular; D010539:Permeability; D004364:Pharmaceutical Preparations / Q000008:administration & dosage* / Q000737:chemistry; D010599:Pharmacokinetics; D011817:Rabbits; D012160:Retina / Q000378:metabolism*; D012590:Sclera / Q000378:metabolism*; D014822:Vitreous Body / Q000378:metabolism
D004364:Pharmaceutical Preparations