A model to predict aqueous humor and plasma pharmacokinetics of ocularly applied drugs.
OBJECTIVE
To develop methods for constructing a pharmacokinetic model to predict the time course of aqueous humor and plasma drug concentrations after topical dosage in rabbits using the simulation program iThink (formerly STELLA; High Performance Systems, Lyme, NH).


METHODS
The model was constructed in experimentally verifiable segments using previously published data on intravenous, nasal, and ocular dosage, and was used to describe the influence of prolonging precorneal retention and varying drug release rate on the ratio of drug absorbed locally to drug absorbed systemically in rabbits.


RESULTS
The model developed is comprehensive; it includes precorneal kinetics, nasal absorption kinetics, and plasma kinetics.


CONCLUSIONS
Such a model may be useful in designing drug delivery strategies to improve the safety of topical eye medications through minimization of systemic absorption and maximization of drug delivery to ocular tissues.
Grass
G M
GM
Precision Instrument Design, Inc., Tahoe City, California.
Lee
V H
VH
D000042:Absorption; D000287:Administration, Topical; D000818:Animals; D001082:Aqueous Humor / Q000378:metabolism*; D003198:Computer Simulation; D003692:Delayed-Action Preparations / Q000493:pharmacokinetics; D016503:Drug Delivery Systems; D008954:Models, Biological; D011817:Rabbits; D013999:Timolol / Q000097:blood / Q000493:pharmacokinetics*
D003692:Delayed-Action Preparations; D013999:Timolol