Prodrugs of nucleoside analogues for improved oral absorption and tissue targeting
- PMID: 17696166
- DOI: 10.1002/jps.21047
Prodrugs of nucleoside analogues for improved oral absorption and tissue targeting
Abstract
Nucleoside analogues are widely used for the treatment of antiviral infections and anticancer chemotherapy. However, many nucleoside analogues suffer from poor oral bioavailability due to their high polarity and low intestinal permeability. In order to improve oral absorption of these polar drugs, prodrugs have been employed to increase lipophilicity by chemical modification of the parent. Alternatively, prodrugs targeting transporters present in the intestine have been exploited to facilitate the transport of the nucleoside analogues. Valacyclovir and valganciclovir are two successful valine ester prodrugs transported by the PepT1 transporter. Recently, research efforts have focused on design of prodrugs for tissue specific delivery to improve efficacy and safety. This review presents advances of prodrug approaches for improved oral absorption of nucleoside analogues and recent developments in tissue targeting.
(Copyright) 2008 Wiley-Liss, Inc.
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