OVERVIEW OF OCULAR ANATOMY, PHYSIOLOGY, AND BIOCHEMISTRY
The eye is a specialized sensory organ that is relatively secluded from systemic access by the blood-retinal, blood-aqueous, and blood-vitreous barriers; as a consequence, the eye exhibits some unusual pharmacodynamic and pharmacokinetic properties. No organ in the body is more accessible or visible for observation; however, the eye also presents some unique opportunities as well as challenges for drug delivery.
PHARMACOKINETICS AND TOXICOLOGY OF OCULAR THERAPEUTIC AGENTS Drug Delivery Strategies
Properties of varying ocular routes of administration are outlined in Table 63-1. Several formulations prolong the time a drug remains on the surface of the eye. These include gels, ointments, solid inserts, soft contact lenses, and collagen shields. Prolonging the time in the cul-de-sac facilitates drug absorption. Ophthalmic gels (e.g., pilocarpine gel) release drugs by diffusion following erosion of soluble polymers. The polymers used include cellulosic ethers, polyvinyl alcohol, carbopol, polyacrylamide, polymethylvinyl ether-maleic anhydride, poloxamer 407, and puronic acid. Ointments usually contain mineral oil and a petrolatum base and are helpful in delivering antibiotics, cycloplegic drugs, or miotic agents. Solid inserts, such as the ganciclovir intravitreal implant, provide a zero-order rate of delivery over several months to treat cytomegalovirus retinitis in patients with AIDS.
Classical pharmacokinetic models of systemically administered drugs (see Chapter 1) do not fully apply to many ophthalmic drugs. Most ophthalmic medications are formulated to be applied topically or may be injected by subconjunctival, sub-Tenon's, and retrobulbar routes (Figure 63-1 and Table 63-1). Although similar principles of absorption, distribution, metabolism, and excretion determine drug disposition in the eye, these alternative routes of drug administration introduce other variables in compartmental analysis.
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