Systematic (IUPAC) name | |
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({[(2R)-1-(6-amino-9H-purin-9-yl)propan-2-yl]oxy}methyl)phosphonic acid | |
Clinical data | |
Trade names | Viread |
AHFS/Drugs.com | monograph |
MedlinePlus | a602018 |
Pregnancy cat. | B (United States) |
Legal status | ℞-only (U.S.), POM (UK) |
Routes | Oral |
Pharmacokinetic data | |
Bioavailability | 25% |
Protein binding | < 1% |
Half-life | 17 hours |
Excretion | Renal |
Identifiers | |
CAS number | 147127-20-6 |
ATC code | J05AF07 |
PubChem | CID 464205 |
DrugBank | APRD01248 |
ChemSpider | 408154 |
UNII | 99YXE507IL |
KEGG | D01982 |
ChEMBL | CHEMBL483 |
Chemical data | |
Formula | C9H14N5O4P |
Mol. mass | 287.213 g/mol |
SMILES | eMolecules & PubChem |
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Tenofovir disoproxil fumarate (TDF or PMPA[1]), marketed by Gilead Sciences under the trade name Viread, belongs to a class of antiretroviral drugs known as nucleotide analogue reverse transcriptase inhibitors (NRTIs), which block reverse transcriptase, an enzyme crucial to viral production.
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Tenofovir disoproxil fumarate is a prodrug form of tenofovir. Tenofovir is also available in a fixed-dose combination with emtricitabine in a product with the brand name Truvada for once-a-day dosing. Atripla, a fixed-dose triple combination of tenofovir, emtricitabine and efavirenz, was approved by the FDA on 12 July 2006 and is now available, providing a single daily dose for the treatment of HIV.
Tenofovir was discovered through a collaborative research effort between Antonín Holý at the Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic (IOCB) in Prague, and Erik DeClercq, Rega Institute for Medical Research, Catholic University of Leuven, Belgium.
Tenofovir was approved by the U.S. Food and Drug Administration (FDA) on October 26, 2001 for the treatment of HIV, and on August 11, 2008 for the treatment of chronic hepatitis B.[2][3]
A difficult step in the manufacture of tenofovir is near the end, when the mixture is "like oatmeal, making it very difficult to stir," said Joseph Fortunak, who left Abbott Laboratories to teach at Howard. That slows the next reaction, a problem because the intermediary is highly unstable and decomposes, thus lowering the yield.
Fortunak's graduate student Adrian Williams tested different methods to improve this step. A catalyst, TBAB (tetrabutylammonium bromide) sped up the reaction and thinned the oatmeal-like mixture into something "like milk," Williams said. But unexpectedly, it made the product more stable, which substantially increased the yield. This lowered the cost by about 20%.[4]
Tenofovir is indicated in combination with other antiretroviral agents for the treatment of HIV-1 infection in adults. This indication is based on analyses of plasma HIV-1 RNA levels and CD4 cell counts in controlled studies of tenofovir in treatment-naive and treatment-experienced adults. There are no study results demonstrating the effect of tenofovir on the clinical progression of HIV. It also has activity against wild-type and lamivudine-resistant HBV.
The most common side effects associated with tenofovir include nausea, vomiting, diarrhea, and asthenia. Less frequent side effects include hepatotoxicity, abdominal pain, and flatulence.[5] Tenofovir has also been implicated in causing renal toxicity, particularly at elevated concentrations.[6]
Tenofovir can cause acute renal failure, Fanconi syndrome, proteinuria or tubular necrosis. These side effects are due to accumulation of the drug in proximal tubules. Tenofovir can interact with didanosine by increasing didanosine's concentration. It also decreases the concentration of atazanavir sulfate.
Tenofovir may be measured in plasma by liquid chromatography. Such testing is useful for monitoring therapy and to prevent drug accumulation and toxicity in patients with renal or hepatic impairment.[7][8][9]
A 2006 trial by Family Health International gave either tenofovir or a placebo to 936 high-risk women in Cameroon, Ghana and Nigeria. While the results show signs that the tenofovir group contracted HIV at a reduced rate, the researchers cautioned against drawing conclusions from the study because the sample size was so small.[10] [11] In July 2010, a vaginal gel containing tenofovir was shown to reduce HIV infection rates by 39 percent in the CAPRISA 004 trial conducted in South Africa.[12]
In July 2011, a placebo-controlled trial in Africa of daily tenofovir was shown to reduce HIV infection rates by 62%. [13]
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