Prodrug and antedrug: two diametrical approaches in designing safer drugs

The prodrug and antedrug concepts, which were developed to overcome the physical and pharmacological shortcomings of various therapeutic classes of agents, employ diametrically different metabolic transformations. The prodrug undergoes a predictable metabolic activation prior to exhibiting its pharm...

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Bibliographic Details
Published in:Archives of pharmacal research 2002-04, Vol.25 (2), p.111-136
Main Authors: Lee, Henry J, Cooperwood, John S, You, Zhengqing, Ko, Dong-Hoon
Format: Article
Language:English
Subjects:
Cytosine Deaminase
Drug Design
Flucytosine - therapeutic use
Ganciclovir - therapeutic use
Genetic Therapy
Immunoconjugates - therapeutic use
Nucleoside Deaminases - genetics
Nucleosides - therapeutic use
Nucleotides - therapeutic use
Prodrugs - therapeutic use
Thymidine Kinase - genetics
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Summary:The prodrug and antedrug concepts, which were developed to overcome the physical and pharmacological shortcomings of various therapeutic classes of agents, employ diametrically different metabolic transformations. The prodrug undergoes a predictable metabolic activation prior to exhibiting its pharmacological effects in a target tissue while the antedrug undergoes metabolic deactivation in the systemic circulation upon leaving a target tissue. An increased therapeutic index is the aspiration for both approaches in designing as well as evaluation criteria. The recent research endeavors of prodrugs include the gene-directed and antibody-directed enzymatic activation of a molecule in a targeted tissue, organ specific delivery, improved bioavailabilities of nucleosides and cellular penetration of nucleotides. As for antedrugs, emphasis in research has been based upon the design and synthesis of systemically inactive molecule by incorporating a metabolically labile functional group into an active molecule.
ISSN:0253-6269
1976-3786
DOI:10.1007/BF02976552