title: Limits on optimizing ocular drug delivery.
abstract: 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.
authors.affiliation: Alcon Laboratories, Inc., Fort Worth, TX 76134-2099.
authors.forename: J C
authors.initials: JC
authors.lastname: Keister
authors.forename: E R
authors.initials: ER
authors.lastname: Cooper
authors.forename: P J
authors.initials: PJ
authors.lastname: Missel
authors.forename: J C
authors.initials: JC
authors.lastname: Lang
authors.forename: D F
authors.initials: DF
authors.lastname: Hager
mesh_terms: 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
chemical_list: D009883:Ophthalmic Solutions