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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 J+Clin+Transl+Hepatol
2013 ; 1
(1
): 33-8
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Advances in Nucleotide Antiviral Development from Scientific Discovery to
Clinical Applications: Tenofovir Disoproxil Fumarate for Hepatitis B
#MMPMID26357604
Lou L
J Clin Transl Hepatol
2013[Sep]; 1
(1
): 33-8
PMID26357604
show ga
Exploration of naturally occurring chemical structures for medicinal uses has
received significant interest in drug discovery and development research in the
past few decades. None have had more success or products of greater clinical
efficacy than synthetic analogs of nucleosides and nucleotides, especially as
antiviral drugs. Nucleos(t)ide antivirals are synthetic analogs of the natural
building blocks of DNA or RNA. This review focuses on the developmental path of
tenofovir disoproxil fumarate (TDF), a prodrug of a nucleotide analog and its
clinical applications as a first-line antiviral for chronic hepatitis B (CHB).
Tenofovir is a potent antiviral compound, but has poor oral availability. The
disoproxil fumarate (DF) prodrug moiety greatly enhances intestinal absorption
allowing it to become an oral medication. Tenofovir is activated intracellularly,
and the incorporation into HBV DNA prevents further elongation thus terminating
replication. In patients with CHB, TDF has demonstrated broad, potent and
sustained virologic response. Maintenance of viral suppression for up to 5 years
resulted in regression of fibrosis and cirrhosis. No tenofovir-resistant HBV
variants have been detected in patients after long-term use. The efficacy and
safety profiles reported from cohort studies of clinical practices were
consistent with those observed in registration trials. Continuous development
includes a new oral prodrug, tenofovir alafenamide fumarate (TAF), which has
enhanced delivery of tenofovir to target cells compared to TDF.