PHARMACOKINETIC MODEL OF INTRAVITREAL DRUG INJECTION

A dynamic mathematical model is developed to describe the distribution and elimination behavior of a drug in the vitreous body following int ravitreal injection. The effects of three elimination pathways-the ann ular gap between the lens and the ciliary body (the posterior chamber) , the lens, and the retina-choroid-sclera membrane-upon the concentrat ion distribution in the vitreous body and the time course of the rate of elimination have been quantitatively demonstrated. The effects of m etabolism in the vitreous body and the site of injection are also simu lated. The annular gap between the lens and the ciliary body (the post erior chamber)is found to be a main route of elimination for large mol ecules injected into the vitreous body. For small or highly lipophilic molecules, however, both the posterior chamber and the retina-choroid -sclera membrane act as major routes of elimination. The lens pathway may contribute negligibly to the escape of drugs from the vitreous bod y. The concentration on the surface of the retina is appreciably affec ted by the site of injection or the initial distribution profiles, whi le the concentration gradient on the lens surface remains almost indep endent of the site of injection. To maintain the therapeutic concentra tion in the vitreous body or in the retina for a prolonged period of t ime, the drug must be injected into the posterior area of the vitreous body. When the drug is injected into the anterior segment of the vitr eous body, the drug molecules quickly escape into the posterior chambe r from the annular gap between the lens and the ciliary body. The pres ent mathematical model describes well in vivo elimination profile of l omefloxacin following intravitreal injection.