Alkoxyalkyl prodrugs of acyclic nucleoside phosphonates enhance oral antiviral activity and reduce toxicity: current state of the art.

ABSTRACT: Although the acyclic nucleoside phosphonates cidofovir, adefovir and tenofovir are approved for treating human cytomegalovirus, hepatitis B and HIV infections, respectively, their utility is limited by low oral bioavailability, renal toxicity and poor cell penetration. Research over the past decade has shown that these undesirable features can be eliminated by esterifying the compounds with an alkoxyalkyl group, in effect disguising them as lysophospholipids. In this modified form, the drugs are readily taken up in the gastrointestinal tract and have a prolonged circulation time in plasma. The active metabolite also has a long half life within cells, permitting infrequent dosing. Because these modified drugs are not recognized by the transport mechanisms that cause the accumulation of acyc

SUBMITTER: Hostetler KY 

PROVIDER: S-EPMC2768545 | biostudies-literature | 2009 May

REPOSITORIES: biostudies-literature