A pharmacokinetic model for ocular drug delivery.
A pharmacokinetic model of ocular drug delivery has been developed for describing the elimination and distribution of ocular drugs in the eye. The model, based on Fick's second law of diffusion, assumes a modified cylindrical eye with three pathways for drug transport across the surface of the eye: the anterior aqueous chamber, the posterior aqueous chamber and the retina/choroids/scleral membrane covering the vitreous body. The model parameters such as the diffusion coefficient and the partition coefficient in various eye tissues can be evaluated from the in vitro membrane penetration experiments using a side-by-side diffusion cell system. The diffusion coefficient for a drug is also predicted by taking account of the effect of the molecular weight of model compounds. The present ocular pharmacokinetic model, which can predict the local concentration distribution in the eye, has well described the in vivo concentration profile in the various eye tissues, the lens, the aqueous humor and the vitreous body, following not only topical eye drop instillation but systemic administration as well. The present model also simulates the effects of binding and metabolism in the eye as well as the individual difference in ocular functions and structure such as cataract surgery and vitreous fluidity on the distribution and elimination of drug molecules in the eye.
Tojo
Kakuji
K
Faculty of Computer Science and Systems Engineering, Kyushu Institute of Technology, Iizuka, Fukuoka 820-8502, Japan. tojo@bio.kyutech.ac.jp
D000287:Administration, Topical; D000818:Animals; D002417:Cattle; D004058:Diffusion; D016503:Drug Delivery Systems / Q000379:methods*; D005123:Eye / Q000187:drug effects / Q000378:metabolism*; D008956:Models, Chemical; D009883:Ophthalmic Solutions / Q000008:administration & dosage / Q000493:pharmacokinetics; D004364:Pharmaceutical Preparations / Q000008:administration & dosage / Q000378:metabolism*; D011485:Protein Binding / Q000187:drug effects / Q000502:physiology; D011817:Rabbits; D013552:Swine
D009883:Ophthalmic Solutions; D004364:Pharmaceutical Preparations