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?:abstract
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Prodrugs are bioreversible, inactive drug derivatives, which have the ability to convert into a parent drug in the body. In the past, prodrugs were used as a last option; however, nowadays, prodrugs are considered already in the early stages of drug development. Optimal prodrug needs to have effective absorption, distribution, metabolism, and elimination (ADME) features to be chemically stable, to be selective towards the particular site in the body, and to have appropriate safety. Traditional prodrug approach aims to improve physicochemical/biopharmaceutical drug properties; modern prodrugs also include cellular and molecular parameters to accomplish desired drug effect and site-specificity. Here, we present recently investigated prodrugs, their pharmaceutical and clinical advantages, and challenges facing the overall prodrug development. Given examples illustrate that prodrugs can accomplish appropriate solubility, increase permeability, provide site-specific targeting (i.e., to organs, tissues, enzymes, or transporters), overcome rapid drug metabolism, decrease toxicity, or provide better patient compliance, all with the aim to provide optimal drug therapy and outcome. Overall, the prodrug approach is a powerful tool to decrease the time/costs of developing new drug entities and improve overall drug therapy.
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