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 unique pharmacodynamic and pharmacokinetic properties.
A number of delivery systems have been developed for treating ocular diseases. Most ophthalmic drugs are delivered in solutions, but for compounds with limited solubility, a suspension form facilitates delivery. Properties of varying ocular routes of administration are outlined in Table 64-1. 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. Ophthalmic gels (eg, pilocarpine 4% 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 pluronic 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 by steady-state diffusion, whereby drug is released at a constant rate over a period of time rather than as a bolus. This surgical implant has been used to deliver anticytomegalovirus (CMV) medication in proximity to the retinal infection. The intent is to deliver a sustained dose of medication over several months with reduced spikes in drug delivery independent of patient compliance.
TABLE 64-1Characteristics of Ocular Routes of Drug Administration |Favorite Table|Download (.pdf) TABLE 64-1Characteristics of Ocular Routes of Drug Administration
|Route ||Absorption Pattern ||Special Utility ||Limitations and Precautions |
|Topical ||Prompt, depending on formulation ||Convenient, economical, relatively safe ||Compliance, corneal and conjunctival toxicity, nasal mucosal toxicity, systemic side effects from nasolacrimal absorption |
|Subconjunctival, sub-Tenon’s, and retrobulbar injections ||Prompt or sustained, depending on formulation ||Anterior segment infections, posterior uveitis, cystoid macular edema ||Local toxicity, tissue injury, globe Perforation, optic nerve trauma, central retinal artery and/or vein occlusion, direct retinal drug toxicity with inadvertent globe perforation, ocular muscle trauma, prolonged drug effect |
|Intraocular (intracameral) injections ||Prompt ||Anterior segment surgery, infections ||Corneal toxicity, intraocular toxicity, relatively short duration of action |
|Intravitreal injection or device ||Absorption circumvented, immediate local effect, potential sustained effect ||Endophthalmitis, retinitis, age-related macular degeneration ||Retinal toxicity |
Pharmacokinetic principles based on studies of systemically administered drugs do not fully apply to all ophthalmic drugs. Although similar principles of absorption, distribution, metabolism, and excretion determine the fate of drug disposition in the eye, alternative routes of drug administration, in addition to oral and intravenous routes, introduce other variables in compartmental analysis.