New ocular drugs are designed with a focus on specificity of action and safety, with delivery systems aimed at improving convenience and therefore patient compliance. Each of the following approaches responds to a specific problem in ocular pharmacokinetics.
Ophthalmic prodrugs are therapeutically inactive derivatives of drug molecules that are designed to be activated by enzymatic systems within the eye in order to improve ocular penetration. These derivatives are usually synthesized by conjugation of a specific promoiety to the parent drug via ester or amide. The ester and amide ophthalmic prodrugs are hydrolyzed by esterase and amidases to the active molecules as they permeate through the cornea or conjunctiva. Permeability across the cornea is also improved by the increased lipid solubility of the prodrug. Prostaglandin analogues are successful examples of this drug delivery strategy. Latanoprost, travoprost, and tafluprost are prostaglandin analogues that interact with the prostaglandin FP receptor. They require hydrolyzation prior to becoming active compounds in the eye.
Valacyclovir hydrochloride is an antiviral prodrug that, when taken orally, is easily absorbed through the gastrointestinal tract and quickly converted to the active form of acyclovir. Likewise, famciclovir is a prodrug of the active antiviral penciclovir.
Excerpted from BCSC 2020-2021 series: Section 2 - Fundamentals and Principles of Ophthalmology. For more information and to purchase the entire series, please visit https://www.aao.org/bcsc.