Description
Tenofovir disoproxil fumarate (tenofovir DF) is the first nucleotide analog reverse
transcriptase inhibitor (NRTI) to be launched in the US as a new oral treatment for HIV
infection. This inhibitor can be prepared in six steps from (S)-glycidol by successive
hydrogenation and intramolecular esterification to give the cyclic carbonate which reacts
with adenine to afford the key hydroxypropyl adenine. The latter is transformed into the
phosphonic acid [(R)-PMPA] condensed with the appropriate carbonate to give the
phosphonic acid diester. Tenofovir DF is a water soluble diester that acts as a prodrug
which is rapidly hydrolyzed to form the free tenofovir (analog of adenosine
monophosphate) that acts only after two intracollular phosphorylation steps as a potent
competitive inhibitor for reverse transcriptase. Tenofovir as the triphosphate form is then
incorporated into DNA and causes DNA chain termination. In contrast to nucleoside
analogs, tenofovir does not require initial intracellular phosphorylation, a limiting factor in
resting cells. Tenofovir DF diffuses rapidly into cells due to its liphophilicity, unlike
tenofovir, which requires an endocytosis transport process. The in vitro anti HIV activity of
the oral prodrug is substantially greater than that of tenofovir alone (up to 100-fold), related
to more rapid/extensive cellular uptake. Despite the fact that the prodrug is rapidly
converted to free tenofovir in plasma after oral absorption, it is suggested that even small
amounts of prodrug can provide enhanced antMral activity. In clinical studies, tenofovir DF
has been shown to reduce the level of HIV in the blood for up to 48 weeks when added to
patient's existing antiretroviral regimens. The drug also reduced viral load even in patients
whose HIV had developed resistance to currently available antiretroviral drugs. Tenofovir
DF is unique in demonstrating efficacy against 3TC (lamivudine)-resistant HIV strains.
Moreover, the long intracellular half-life (from 12 to 50h) of the tefonovir diphosphate
allowing for once daily dosing is probably an important factor in the efficacy of this drug/n
vivo. The drug is eliminated by the kidney, is not metabolized by the liver and is not
associated with P450 interactions. The bioavailability of the prodrug was increased
significantly when taken with food from 27 to 40%. The oral bioavailabilty of tenofovir is
< 10%.
Chemical Properties
White Solid
Originator
Gilead Sciences (US)
Uses
Acyclic phosphonate nucleotide analogue; reverse transcriptase inhibitor. Used as an anti-HIV agent. Antiviral.
Uses
An acyclic phosphonate nucleotide analog and selective HIV-1 RT inhibitor
Uses
tyrosinase inhibitor used for skin lightening and anti-melasma
Definition
ChEBI: A fumarate salt prepared from equimolar amounts of tenofovir disoproxil and fumaric acid. It is used in combination therapy for the treatment of HIV infection.
Brand name
Viread (Gilead Sciences).
General Description
Pharmaceutical secondary standards for application in quality control provide pharma laboratories and manufacturers with a convenient and cost-effective alternative to the preparation of in-house working standards
Biochem/physiol Actions
Tenofovir disoproxil fumarate is a prodrug of tenofovir, a nucleotide analogue reverse transcriptase inhibitor (nRTI) that causes premature termination of DNA transcription. In a T cell line and primary blood lymphocytes, the antiviral activity of tenofovir disoproxil was shown to be more than 100-fold greater than tenofovir because of its rapid intracellular uptake. Tenofovir disoproxil fumarate has been used alone and in various combinations for the prevention and treatment of HIV/AIDS and chronic hepatitis B infections and is on the World Health Organization′s List of Essential Medicines.
