Limits on optimizing ocular drug delivery.
The problem of optimizing ocular bioavailability of topically applied ophthalmic drugs is discussed. A formula for drug concentration in the tear film is derived using well-known pharmacokinetic relationships and a first-order drug decay model for the tear film. The time integral of the tear film concentration is then related to ocular bioavailability. The results of this analysis show that: (1) high corneal permeability (corresponding to lipophilic compounds) produces the highest bioavailability; (2) the bioavailability of drugs with high corneal permeability is relatively unaffected by drug volume; and (3) by making the dosage volume sufficiently small, a bioavailability improvement factor of approximately 4 can be obtained for drugs with low corneal permeability.
Keister
J C
JC
Alcon Laboratories, Inc., Fort Worth, TX 76134-2099.
Cooper
E R
ER
Missel
P J
PJ
Lang
J C
JC
Hager
D F
DF
D000287:Administration, Topical; D001682:Biological Availability; D003315:Cornea / Q000378:metabolism*; D006801:Humans; D007322:Instillation, Drug; D008433:Mathematics; D008954:Models, Biological; D009883:Ophthalmic Solutions / Q000493:pharmacokinetics*; D010539:Permeability
D009883:Ophthalmic Solutions