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 intravitreal injection. The effects of three elimination pathways--the annular gap between the lens and the ciliary body (the posterior chamber), the lens, and the retina-choroid-sclera membrane--upon the concentration distribution in the vitreous body and the time course of the rate of elimination have been quantitatively demonstrated. The effects of metabolism in the vitreous body and the site of injection are also simulated. The annular gap between the lens and the ciliary body (the posterior chamber) is found to be a main route of elimination for large molecules 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 body. The concentration on the surface of the retina is appreciably affected by the site of injection or the initial distribution profiles, while the concentration gradient on the lens surface remains almost independent of the site of injection. To maintain the therapeutic concentration in the vitreous body or in the retina for a prolonged period of time, the drug must be injected into the posterior area of the vitreous body. When the drug is injected into the anterior segment of the vitreous body, the drug molecules quickly escape into the posterior chamber from the annular gap between the lens and the ciliary body. The present mathematical model describes well in vivo elimination profile of lomefloxacin following intravitreal injection.