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Investigative Ophthalmology & Visual Science, Vol 34, 2251-2259, Copyright © 1993 by Association for Research in Vision and Ophthalmology

ARTICLES AND REPORTS

A model to predict aqueous humor and plasma pharmacokinetics of ocularly applied drugs

GM Grass and VH Lee
Precision Instrument Design, Inc., Tahoe City, California.

PURPOSE. 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). METHOD. 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.




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Copyright © 1993 by the Association for Research in Vision and Ophthalmology