Use of mdck cell line to predict corneal penetration of drugs

Abstract

A new method of evaluating the ability of drug molecules to penetrate the cornea is described. The permeation rate of the drug molecules in MDCK cells is utilized to predict the ability of the molecules to penetrate the cornea. The method is useful for in vitro screening of potential new ophthalmic drugs, as well as in the design of new drug molecules for topical ocular administration.

1 . A method of designing new drug molecules for treating one or more ophthalmic conditions comprising:
 determining the permeation rate of a drug molecule in MDCK cells and converting said permeation rate to a predicted corneal penetration rate by means of a suitable quadratic equation; and   identifying drug molecules having optimum ocular penetration properties using said predicted corneal penetration rate.   
     
     
         2 . A method according to  claim 1  wherein said penetration rate of a drug molecule is converted to said predicted corneal penetration rate by means of the following equation:
   Corneal Permeability=5.41(MDCK Permeability)−0.01(MDCK Permeability) 2 .   
     
     
         3 . A method of treating one or more ocular conditions via topical application of a drug molecule to the affected eye, wherein the design of said drug molecule was based in part on a method of  claim 1 . 
     
     
         4 . A method according to  claim 3  wherein said penetration rate of a drug molecule is converted to said predicted corneal penetration rate by means of the following equation:
   Corneal Permeability=5.41(MDCK Permeability)−0.01(MDCK Permeability) 2 .   
     
     
         5 . A drug molecule designed in part by means of a method comprising:
 determining the permeation rate of a drug molecule in MDCK cells and converting said permeation rate to a predicted corneal penetration rate by means of a suitable quadratic equation; and   identifying drug molecules having optimum ocular penetration properties using said predicted corneal penetration rate.   
     
     
         6 . A drug molecule of  claim 5  according to  claim 3  wherein said penetration rate is converted to said predicted corneal penetration rate by means of the following equation:
   Corneal Permeability=5.41(MDCK Permeability)−0.01(MDCK Permeability) 2 .   
     
     
         7 . A method of treating one or more ocular conditions via topical application of a drug molecule to the affected eye, wherein the selection of said drug molecule was based in part on a method of evaluating the corneal permeability of a drug molecule, said method of evaluating comprising:
 determining the permeation rate of a drug molecule in MDCK cells and converting said permeation rate to a predicted corneal penetration rate by means of a suitable quadratic equation.   
     
     
         8 . A method according to  claim 7  wherein said penetration rate of a drug molecule is converted to said predicted corneal penetration rate by means of the following equation:
   Corneal Permeability=5.41(MDCK Permeability)−0.01(MDCK Permeability) 2 .