ABSTRACT
Prodrug design has been widely used as a successful approach to achieve selectivity, reduce toxicity, and improve pharmaceutical, pharmacokinetic, and pharmacodynamics features of drugs for some time. The prodrug approach offers enormous applicability as it overcomes several barriers in their applications, including poor aqueous solubility, local irritation after application, inadequate permeability and bioavailability, chemical instability, fast presystemic metabolism, and inappropriate physicochemical characteristics of the drug, among others. Phosphate esters have been used widely to design water-soluble prodrugs as the dianionic phosphate group in their structures is able to increase water-solubility by several orders of magnitude. Prodrugs containing an imine function may also be explored for increasing the water-solubility of compounds. The valproic acid-taurine prodrug exhibited anticonvulsant activity with reduced teratogenicity, demonstrating that, in addition to the increased water-solubility, the adverse effects of the parent drug may also be modulated by using the prodrug approach.
