Wikipedia:WikiProject Chemicals/Chembox validation/VerifiedDataSandbox and Tenofovir disoproxil: Difference between pages

{{Short description|Antiviral drug used to treat or prevent HIV and hepatitis infections}}

{{Redirect|Tenofovir|the newer tenofovir prodrug|Tenofovir alafenamide}}

{{Use dmy dates|date=May 2024}}

{{cs1 config |name-list-style=vanc |display-authors=6}}

{{Infobox drug

| image = Tenofovir disoproxil structure.svg

| width = 260

| alt =

<!--Clinical data-->

| pronounce = {{IPAc-en|ˌ|t|ə|ˈ|n|oʊ|f|ə|v|ɪər|_|ˌ|d|ɪ|s|ə|ˈ|p|r|ɑː|k|s|əl}}

| tradename = Viread, others

| Drugs.com = {{drugs.com|monograph|tenofovir-disoproxil-fumarate}}

| MedlinePlus = a602018

| DailyMedID = Tenofovir disoproxil

| pregnancy_AU = B3

| routes_of_administration = [[Oral administration|By mouth]]

| class =

| ATC_prefix = J05

| ATC_suffix = AF07

| legal_AU = S4

| legal_AU_comment = <ref>{{cite web | title=Prescription medicines: registration of new generic medicines and biosimilar medicines, 2017 | website=Therapeutic Goods Administration (TGA) | date=21 June 2022 | url=https://www.tga.gov.au/resources/publication/publications/prescription-medicines-registration-new-generic-medicines-and-biosimilar-medicines-2017 | access-date=30 March 2024}}</ref>

| legal_CA = Rx-only

| legal_UK = POM

| legal_US = Rx-only

| legal_EU = Rx-only

| legal_EU_comment = <ref>{{cite web | title=Viread EPAR | website=[[European Medicines Agency]] (EMA) | date=5 February 2002 | url=https://www.ema.europa.eu/en/medicines/human/EPAR/viread | access-date=25 May 2024}}</ref>

<!-- Pharmacokinetic data -->

| bioavailability = 25%

| protein_bound =

| metabolism = [[Ester hydrolysis]]

| metabolites = Tenofovir

| onset =

| elimination_half-life =

| duration_of_action =

| excretion =

<!-- Identifiers -->

| CAS_number = 201341-05-1

| PubChem = 5481350

| DrugBank = DB00300

| ChemSpiderID = 4587262

| UNII = F4YU4LON7I

| KEGG = C13480

| ChEBI = 63717

| ChEMBL = 1538

| NIAID_ChemDB = 080741

| synonyms = Bis(POC)PMPA

<!-- Chemical data -->

| IUPAC_name = Bis{[(isopropoxycarbonyl)oxy]methyl} ({[(2''R'')-1-(6-amino-9''H''-purin-9-yl)-2-propanyl]oxy}methyl)phosphonate

| C = 19 | H = 30 | N = 5 | O = 10 | P = 1

| SMILES = C[C@H](Cn1cnc2c1ncnc2N)OCP(=O)(OCOC(=O)OC(C)C)OCOC(=O)OC(C)C

| StdInChI=1S/C19H30N5O10P/c1-12(2)33-18(25)28-9-31-35(27,32-10-29-19(26)34-13(3)4)11-30-14(5)6-24-8-23-15-16(20)21-7-22-17(15)24/h7-8,12-14H,6,9-11H2,1-5H3,(H2,20,21,22)/t14-/m1/s1

| StdInChIKey = JFVZFKDSXNQEJW-CQSZACIVSA-N

}}

| drug_name = Tenofovir

| Watchedfields = changed

| verifiedrevid = 461742056

| image = Tenofovir.svg

| width =

| alt =

| routes_of_administration =

| ATC_prefix = None

| ATC_suffix =

| metabolism = [[Phosphorylation]]

| metabolites = Tenofovir diphosphate ([[active metabolite]])

| excretion = [[Kidney]]

| DrugBank =

| KEGG_Ref = {{keggcite||kegg}}

| KEGG =

| ChEBI = 63625

| synonyms = 9-(2-Phosphonyl-methoxypropyly)adenine (PMPA)

| IUPAC_name = ({[(2''R'')-1-(6-amino-9''H''-purin-9-yl)propan-2-yl]oxy}methyl)phosphonic acid

| C=9 | H=14 | N=5 | O=4 | P=1

<!-- Definition and uses -->

'''Tenofovir disoproxil''', sold under the brand name '''Viread''' among others, is a medication used to treat chronic [[hepatitis B]] and to prevent and treat [[HIV/AIDS]].<ref name=AHFS2016/> It is generally recommended for use with other antiretrovirals.<ref name=AHFS2016/> It may be used for prevention of HIV/AIDS among those at high risk before exposure, and after a [[needlestick injury]] or other potential exposure.<ref name=AHFS2016/> It is sold both by itself and together in combinations such as [[emtricitabine/tenofovir]], [[efavirenz/emtricitabine/tenofovir]],<ref name=AHFS2016/> and [[elvitegravir/cobicistat/emtricitabine/tenofovir]].<ref>{{cite web |title=Stribild | work = PubChem | publisher = U.S. National Library of Medicine |url=https://pubchem.ncbi.nlm.nih.gov/compound/Stribild |access-date=6 February 2022}}</ref> It does not cure HIV/AIDS or hepatitis B.<ref name=AHFS2016/><ref>{{cite journal | vauthors = Martin P, Lau DT, Nguyen MH, Janssen HL, Dieterich DT, Peters MG, Jacobson IM | title = A Treatment Algorithm for the Management of Chronic Hepatitis B Virus Infection in the United States: 2015 Update | journal = Clinical Gastroenterology and Hepatology | volume = 13 | issue = 12 | pages = 2071–87.e16 | date = November 2015 | pmid = 26188135 | doi = 10.1016/j.cgh.2015.07.007 }}</ref> It is available by mouth as a tablet or powder.<ref name=AHFS2016>{{cite web|title=Tenofovir Disoproxil Fumarate|url=https://www.drugs.com/monograph/tenofovir-disoproxil-fumarate.html|publisher=The American Society of Health-System Pharmacists|access-date=29 November 2016|url-status=live|archive-url=https://web.archive.org/web/20161130111916/https://www.drugs.com/monograph/tenofovir-disoproxil-fumarate.html|archive-date=30 November 2016}}</ref>

<!-- Side effects and mechanism -->

Common side effects include nausea, rash, diarrhea, headache, pain, depression, and weakness.<ref name=AHFS2016/> Severe side effects include [[lactic acidosis|high blood lactate]] and an [[hepatomegaly|enlarged liver]].<ref name=AHFS2016/> There are no absolute contraindications.<ref name=AHFS2016/> It is often recommended during [[pregnancy]] and appears to be safe.<ref name=AHFS2016/> It is a [[Reverse-transcriptase inhibitor|nucleotide reverse transcriptase inhibitor]] and works by decreasing the ability of the viruses to replicate.<ref name=AHFS2016/>

<!-- History and culture -->

Tenofovir was patented in 1996 and approved for use in the United States in 2001.<ref>{{cite book| vauthors = Fischer J, Ganellin CR |title=Analogue-based Drug Discovery|date=2006|publisher=John Wiley & Sons|isbn=9783527607495|page=505|url=https://books.google.com/books?id=FjKfqkaKkAAC&pg=PA505|language=en|url-status=live|archive-url=https://web.archive.org/web/20170908213935/https://books.google.com/books?id=FjKfqkaKkAAC&pg=PA505|archive-date=8 September 2017}}</ref> It is on the [[WHO Model List of Essential Medicines|World Health Organization's List of Essential Medicines]].<ref name="WHO21st">{{cite book | vauthors = ((World Health Organization)) | title = World Health Organization model list of essential medicines: 21st list 2019 | year = 2019 | hdl = 10665/325771 | author-link = World Health Organization | publisher = World Health Organization | location = Geneva | id = WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO | hdl-access=free }}</ref> It is available in the United States as a [[generic medication]] as of 2017.<ref>{{cite web |title=Teva Announces Exclusive Launch of a Generic version of Viread in the United States |url=https://www.tevapharm.com/news/teva_announces_exclusive_launch_of_generic_viread_in_the_united_states_12_17.aspx |website=www.tevapharm.com |access-date=6 November 2018 |archive-date=6 November 2018 |archive-url=https://web.archive.org/web/20181106132154/https://www.tevapharm.com/news/teva_announces_exclusive_launch_of_generic_viread_in_the_united_states_12_17.aspx |url-status=dead }}</ref>

==Medical uses==

Tenofovir disoproxil is used for HIV-1 infection and chronic hepatitis B treatment. For HIV-1 infection, tenofovir is indicated in combination with other antiretroviral agents for people 2 years of age and older. For chronic hepatitis B patients, tenofovir is indicated for patients 12 years of age and older.<ref name="prescribing_info">{{cite web | work = Gilead Sciences, Inc. | url = http://www.gilead.com/pdf/viread_pi.pdf | title = Tenofovirdisoproxil Prescribing Information. | archive-url = https://web.archive.org/web/20130207072249/http://www.gilead.com/pdf/viread_pi.pdf | archive-date = 7 February 2013| date = November 2012 }}</ref>

===HIV risk reduction===

Tenofovir can be used for HIV prevention in people who are at high risk for infection through sexual transmission or injecting drug use. A [[Cochrane review]] examined the use of tenofovir for prevention of HIV [[pre-exposure prophylaxis|before exposure]] and found that both tenofovir alone and the [[tenofovir/emtricitabine]] combination decreased the risk of contracting HIV for high risk patients.<ref>{{cite journal | vauthors = Okwundu CI, Uthman OA, Okoromah CA | title = Antiretroviral pre-exposure prophylaxis (PrEP) for preventing HIV in high-risk individuals | journal = The Cochrane Database of Systematic Reviews | volume = 7 | issue = 7 | pages = CD007189 | date = July 2012 | pmid = 22786505 | doi = 10.1002/14651858.CD007189.pub3 }}</ref> The U.S. [[Centers for Disease Control and Prevention]] (CDC) also conducted a study in partnership with the [[Ministry of Public Health (Thailand)|Thailand Ministry of Public Health]] to ascertain the effectiveness of providing people who inject drugs illicitly with daily doses of tenofovir as a [[HIV/AIDS in Thailand|prevention measure]]. The results revealed a 48.9% reduced incidence of the virus among the group of subjects who received the drug in comparison to the control group who received a [[placebo]].<ref>{{cite web|title=Preventive drug could reduce HIV transmission among injecting drug users|url=https://theconversation.com/preventive-drug-could-reduce-hiv-transmission-among-injecting-drug-users-15166|work=The Conversation Australia|publisher=The Conversation Media Group|access-date=17 June 2013| vauthors = Bourke E |date=14 June 2013|url-status=live|archive-url=https://web.archive.org/web/20131101033500/https://theconversation.com/preventive-drug-could-reduce-hiv-transmission-among-injecting-drug-users-15166|archive-date=1 November 2013}}</ref>

==Adverse effects==

Tenofovir disoproxil is generally well tolerated with low discontinuation rates among the HIV and chronic hepatitis B population.<ref name=":0">{{cite journal | vauthors = Ustianowski A, Arends JE | title = Tenofovir: What We Have Learnt After 7.5&nbsp;Million Person-Years of Use | journal = Infectious Diseases and Therapy | volume = 4 | issue = 2 | pages = 145–57 | date = June 2015 | pmid = 26032649 | pmc = 4471058 | doi = 10.1007/s40121-015-0070-1 }}</ref> There are no contraindications for use of this drug.<ref name="prescribing_info" /> The most commonly reported side effects due to use of tenofovir disoproxil were dizziness, nausea, and diarrhea.<ref name=":0" /> Other adverse effects include depression, sleep disturbances, headache, itching, rash, and fever. The US [[boxed warning]] cautions potential onset of [[lactic acidosis]] or liver damage due to use of tenofovir disoproxil.<ref>{{Cite web|url=https://medlineplus.gov/druginfo/meds/a602018.html|title=Tenofovir: MedlinePlus Drug Information|work = MedlineP | publisher = U.S. National Library of Medicine |access-date=9 November 2016|url-status=live|archive-url=https://web.archive.org/web/20161110105928/https://medlineplus.gov/druginfo/meds/a602018.html|archive-date=10 November 2016}}</ref>

Long term use of tenofovir disoproxil is associated with [[nephrotoxicity]] and bone loss. Presentation of nephrotoxicity can appear as [[Fanconi syndrome]], acute kidney injury, or decline of [[glomerular filtration rate]] (GFR).<ref>{{cite journal | vauthors = Morlat P, Vivot A, Vandenhende MA, Dauchy FA, Asselineau J, Déti E, Gerard Y, Lazaro E, Duffau P, Neau D, Bonnet F, Chêne G | title = Role of traditional risk factors and antiretroviral drugs in the incidence of chronic kidney disease, ANRS CO3 Aquitaine cohort, France, 2004-2012 | journal = PLOS ONE | volume = 8 | issue = 6 | pages = e66223 | date = 12 June 2013 | pmid = 23776637 | pmc = 3680439 | doi = 10.1371/journal.pone.0066223 | bibcode = 2013PLoSO...866223M | doi-access = free }}</ref> Discontinuation of tenofovir disoproxil can potentially lead to reversal of renal impairment. Nephrotoxicity may be due to proximal tubules accumulation of Tenofovir disoproxil leading to elevated serum concentrations.<ref name=":0" />

== Interactions ==

Tenofovir interacts with [[didanosine]] and HIV-1 protease inhibitors. Tenofovir increases didanosine concentrations and can result in adverse effects such as [[pancreatitis]] and [[Peripheral neuropathy|neuropathy]]. Tenofovir also interacts with HIV-1 protease inhibitors such as [[atazanavir]], by decreasing atazanavir concentrations while increasing tenofovir concentrations.<ref name="prescribing_info" /> In addition, since tenofovir is excreted by the kidney, medications that impair renal function can also cause problems.<ref name="AC">{{cite book|title=Austria-Codex|editor=Haberfeld, H|publisher=Österreichischer Apothekerverlag|location=Vienna|year=2015|language=German}}</ref>

==Pharmacology==

===Mechanism of action===

Tenofovir disoproxil is a [[Reverse-transcriptase inhibitor#Nucleotide analog reverse-transcriptase inhibitors .28NtARTIs or NtRTIs.29|nucleotide analog reverse-transcriptase inhibitor]] (NtRTI).<ref name="Drugbank" /> It selectively inhibits viral [[reverse transcriptase]], a crucial enzyme in retroviruses such as [[HIV|human immunodeficiency virus (HIV)]], while showing limited inhibition of human enzymes, such as [[DNA polymerase]]s α, β, and [[mitochondrial DNA]] polymerase γ.<ref name="prescribing_info" /><ref name="Drugbank">{{cite web | work = DrugBank | url = http://www.drugbank.ca/drugs/DB00300 | title = Tenofovir | archive-url = https://web.archive.org/web/20150908115226/http://www.drugbank.ca/drugs/DB00300 | archive-date = 8 September 2015 }}</ref> In vivo tenofovir disoproxil fumarate is converted to tenofovir, an acyclic analog of deoxyadenosine 5'-monophosphate (dAMP).

Tenofovir lacks a hydroxyl group in the position corresponding to the 3' carbon of the dAMP, preventing the formation of the 5′ to 3′ [[phosphodiester bond|phosphodiester]] linkage essential for DNA chain elongation.<ref name="Drugbank" /> Once incorporated into a growing DNA strand, tenofovir causes premature termination of DNA transcription, preventing viral replication.<ref name="Drugbank" />

===Pharmacokinetics===

Tenofovir disoproxil is a [[prodrug]] that is quickly absorbed from the gut and cleaved to release tenofovir.<ref name="prescribing_info" /> Inside cells, tenofovir is [[phosphorylate]]d to tenofovir diphosphate (which is analogous to a ''tri''phosphate, as tenofovir itself already has one [[phosphonate]] residue), the active compound that inhibits reverse transcriptase via chain termination.<ref name="AC" /><ref name="Drugbank" />

In fasting persons, [[bioavailability]] is 25%, and highest [[blood plasma]] concentrations are reached after one hour.<ref name="Drugbank" /> When taken with fatty food, highest plasma concentrations are reached after two hours, and the [[area under the curve (pharmacokinetics)|area under the curve]] is increased by 40%.<ref name="Drugbank" /> It is an inhibitor of [[cytochrome P450]] 1A2.<ref>{{Cite web|url=https://pubchem.ncbi.nlm.nih.gov/compound/5481350#section=DrugBank-Interactions&fullscreen=true|title=Tenofovir disoproxil| work = Pubchem | publisher = U.S. National Library of Medicine |language=en|access-date=17 April 2018}}</ref>

Tenofovir is mainly excreted via the kidneys, both by [[glomerular filtration]] and by [[tubular secretion]] using the transport proteins [[OAT1]], [[OAT3]] and [[ABCC4]].<ref name="AC" />

===Detection in body fluids===

Tenofovir may be measured in plasma by liquid chromatography. Such testing is useful for monitoring therapy and to prevent drug accumulation and toxicity in people with kidney or liver problems.<ref>{{cite journal | vauthors = Delahunty T, Bushman L, Robbins B, Fletcher CV | title = The simultaneous assay of tenofovir and emtricitabine in plasma using LC/MS/MS and isotopically labeled internal standards | journal = Journal of Chromatography B | volume = 877 | issue = 20–21 | pages = 1907–14 | date = July 2009 | pmid = 19493710 | pmc = 2714254 | doi = 10.1016/j.jchromb.2009.05.029 }}</ref><ref>{{cite journal | vauthors = Kearney BP, Yale K, Shah J, Zhong L, Flaherty JF | title = Pharmacokinetics and dosing recommendations of tenofovir disoproxil fumarate in hepatic or renal impairment | journal = Clinical Pharmacokinetics | volume = 45 | issue = 11 | pages = 1115–24 | year = 2006 | pmid = 17048975 | doi = 10.2165/00003088-200645110-00005 | s2cid = 6322957 }}</ref><ref>{{cite book | vauthors = Baselt R | title = Disposition of Toxic Drugs and Chemicals in Man | edition = 8th | publisher = Biomedical Publications | location = Foster City, California | date = 2008 | pages = 1490–1492 }}</ref>

== Chemistry ==

Tenofovir is a derivative of [[adenine]] and this was the chemical starting point for its first published synthesis<ref>{{cite journal |doi=10.1135/cccc19823447 |title=Preparation of 5'-O-phosphonylmethyl analogues of nucleoside-5'-phosphates, 5'-diphosphates and 5'-triphosphates |year=1982 | vauthors = Holý A, Rosenberg I |journal=Collection of Czechoslovak Chemical Communications |volume=47 |issue=12 |pages=3447–3463 }}</ref> which was included in patents to the compound.<ref name=US4808716>{{cite patent |country=US |number=4808716 |status=patent |pubdate=1989-02-28 |fdate=1986-04-25 |pridate=1985-04-25 | inventor = Holy A, Rosenberg I |title=9-(phosponylmethoxyalkyl) adenines, the method of preparation and utilization thereof |assign1=Czech Academy of Sciences }}</ref> During drug development, attention switched to the [[phosphonate]] [[ester]] derivative, tenofovir disoproxil, which was the subject of extensive process chemistry to provide a viable manufacturing route.

:[[File:Tenofovir disoproxil synthesis.svg|650px]]

Adenine is first reacted with a [[Chirality (chemistry)|chiral]] version of [[propylene carbonate]] with ''R'' [[absolute configuration]], using sodium hydroxide as [[Base (chemistry)|base]]. Under these conditions, the reaction is [[regioselective]], with [[alkylation]] occurring exclusively in the [[imidazole]] ring and at the [[Steric_effects#Steric_hindrance|less-hindered]] carbon of the [[dioxolane]]. In the second step, the [[hydroxyl group]] is reacted with a phosphonic acid derivative, using [[tert-Butyllithium|''tert''-butyllithium]] as base to ensure selective O-alkylation, with the formation of an [[ether]] bond. Tenofovir is formed when the diethyl phosphonate group is converted to its acid using [[trimethylsilyl chloride]] in the presence of sodium bromide, a further refinement of the original manufacturing route.<ref name=OPC>{{cite journal |doi=10.1021/op1001337 |title=Process Improvements for the Manufacture of Tenofovir Disoproxil Fumarate at Commercial Scale |year=2010 | vauthors = Brown Ripin DH, Teager DS, Fortunak J, Basha SM, Bivins N, Boddy CN, Byrn S, Catlin KK, Houghton SR, Jagadeesh ST, Kumar KA, Melton J, Muneer S, Rao LN, Rao RV, Ray PC, Reddy NG, Reddy RM, Shekar KC, Silverton T, Smith DT, Stringham RW, Subbaraju GV, Talley F, Williams A |journal=Organic Process Research & Development |volume=14 |issue=5 |pages=1194–1201 }}</ref><ref>{{cite journal |doi=10.1016/j.tet.2010.08.037 |title=Rapid, mild method for phosphonate diester hydrolysis: Development of a one-pot synthesis of tenofovir disoproxil fumarate from tenofovir diethyl ester |year=2010 | vauthors = Houghton SR, Melton J, Fortunak J, Brown Ripin DH, Boddy CN |journal=Tetrahedron |volume=66 |issue=41 |pages=8137–8144 }}</ref><ref>{{cite book |doi=10.1016/B978-0-12-411492-0.00034-1 |doi-access=free |chapter=34: Antiviral Drugs |title=Synthesis of Best-Seller Drugs |year=2016 | vauthors = Vardanyan R, Hruby V |pages=714–716 |isbn=9780124114920 |s2cid=75449475 }}</ref> The synthesis of the alternative ester in tenofovir disoproxil is completed by alkylation with the appropriate [[Chloromethyl group|chloromethyl ether]] derivative and this may be purified as its [[fumarate]] salt.<ref name=OPC/>

==History==

Tenofovir was initially synthesized by [[Antonín Holý]] at the Institute of Organic Chemistry and Biochemistry of the [[Czechoslovak Academy of Sciences]] in [[Prague]]. The patent filed in 1986 makes no mention of the potential use of the compound for the treatment of HIV infection but claims activity against [[herpes simplex]] virus.<ref name=US4808716/>

In 1985, De Clercq and Holý described the activity of PMPA against HIV in cell culture.<ref>{{cite patent |inventor = De Clercq E, Holy A, Rosenberg I |pridate=1985-04-25 |title=Therapeutical application of phosphonylmethoxyalkyl adenines |country=US |patent-number=4724233}}</ref> Shortly thereafter, a collaboration with the biotechnology company [[Gilead Sciences]] led to the investigation of PMPA's potential as a treatment for HIV infected patients. In 1997 researchers from Gilead and the University of California, San Francisco demonstrated that tenofovir exhibits anti-HIV effects in humans when dosed by subcutaneous injection.<ref>{{cite journal | vauthors = Deeks SG, Barditch-Crovo P, Lietman PS, Hwang F, Cundy KC, Rooney JF, Hellmann NS, Safrin S, Kahn JO | title = Safety, pharmacokinetics, and antiretroviral activity of intravenous 9-[2-(R)-(Phosphonomethoxy)propyl]adenine, a novel anti-human immunodeficiency virus (HIV) therapy, in HIV-infected adults | journal = Antimicrobial Agents and Chemotherapy | volume = 42 | issue = 9 | pages = 2380–4 | date = September 1998 | pmid = 9736567 | pmc = 105837 | doi = 10.1128/aac.42.9.2380}}</ref>

The initial form of tenofovir used in these studies had limited potential for widespread use because it poorly penetrated cells and was not absorbed when given by mouth. Gilead developed a pro-drug version of tenofovir, tenofovir disoproxil. This version of tenofovir is often referred to simply as "tenofovir". In this version of the drug, the two negative charges of the tenofovir phosphonic acid group are masked, thus enhancing oral absorption.

Tenofovir disoproxil was approved in the U.S. in 2001, for the treatment of HIV, and in 2008, for the treatment of [[chronic (medical)|chronic]] [[hepatitis B]].<ref>{{cite web | vauthors = Shwiff K | url = https://www.fda.gov/cder/foi/appletter/2008/021356s025ltr.pdf | title = FDA letter of approval (regarding treatment of hepatitis B) | website = [[Food and Drug Administration]] | archive-url = https://web.archive.org/web/20090225093217/https://www.fda.gov/cder/foi/appletter/2008/021356s025ltr.pdf | archive-date= 25 February 2009 }}</ref><ref>{{cite news | url = https://www.wsj.com/articles/SB121849463154631469?mod=us_business_whats_news | title = FDA Clears Viread for Hepatitis B | work = The Wall Street Journal | date = 11 August 2008 | publisher = Dow Jones & Company, Inc. | archive-url = https://web.archive.org/web/20170908215010/https://www.wsj.com/articles/SB121849463154631469?mod=us_business_whats_news | archive-date = 8 September 2017 | last1 = Shwiff | first1 = Kathy }}</ref>

==Drug forms==

Tenofovir disoproxil can be taken [[Oral administration|by mouth]] and is sold under the brand name Viread, among others.<ref name=":1">{{Cite web|url=http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm?fuseaction=Search.SearchAction&SearchTerm=tenofovir&SearchType=BasicSearch|title=Drugs@FDA: FDA Approved Drug Products|website=www.accessdata.fda.gov|access-date=9 November 2016|url-status=live|archive-url=https://web.archive.org/web/20161110045006/http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm?fuseaction=Search.SearchAction&SearchTerm=tenofovir&SearchType=BasicSearch|archive-date=10 November 2016}}</ref> Tenofovir disoproxil is a [[pro-drug]] form of tenofovir phosphonate, which is liberated intracellularly and converted to tenofovir disphophate.<ref>{{cite journal | vauthors = Mouton JP, Cohen K, Maartens G | title = Key toxicity issues with the WHO-recommended first-line antiretroviral therapy regimen | journal = Expert Review of Clinical Pharmacology | volume = 9 | issue = 11 | pages = 1493–1503 | date = November 2016 | pmid = 27498720 | doi = 10.1080/17512433.2016.1221760 | s2cid = 205930751 }}</ref> It is marketed by [[Gilead Sciences]] (as the [[fumarate]], abbreviated TDF).<ref>{{cite journal | vauthors = Emau P, Jiang Y, Agy MB, Tian B, Bekele G, Tsai CC | title = Post-exposure prophylaxis for SIV revisited: animal model for HIV prevention | journal = [[AIDS Research and Therapy]] | volume = 3 | pages = 29 | date = November 2006 | pmid = 17132170 | pmc = 1687192 | doi = 10.1186/1742-6405-3-29 | doi-access = free }}</ref>

Tenofovir disoproxil is also available in pills which combine a number of antiviral drugs into a single dose. Well-known combinations include [[Efavirenz/emtricitabine/tenofovir|Atripla]] (tenofovir disoproxil/emtricitabine/efavirenz), [[Complera]] (tenofovir disoproxil/emtricitabine/rilpivirine), [[Elvitegravir/cobicistat/emtricitabine/tenofovir|Stribild]] (tenofovir disoproxil/emtricitabine/elvitegravir/cobicistat), and [[Tenofovir/emtricitabine|Truvada]] (tenofovir disoproxil/emtricitabine).<ref name=":1" />

Gilead has created a second pro-drug form of the active drug, tenofovir diphosphate, called [[tenofovir alafenamide]]. It differs from tenofovir disoproxil due to its activation in the [[lymphoid cells]]. This allows the active metabolites to accumulate in those cells, leading to lower systemic exposure and potential toxicities.<ref name=":0" />

== References ==

{{reflist}}

{{Microbicides for sexually transmitted diseases}}

{{Antiretroviral drug}}

{{DNA antivirals}}

{{Portal bar | Medicine | Viruses }}

{{Authority control}}

{{DEFAULTSORT:Tenofovir Disoproxil}}

[[Category:Carbonate esters]]

[[Category:Gilead Sciences]]

[[Category:Hepatotoxins]]

[[Category:Isopropyl esters]]

[[Category:Microbicides]]

[[Category:Nucleoside analog reverse transcriptase inhibitors]]

[[Category:Prodrugs]]

[[Category:Purines]]

[[Category:World Health Organization essential medicines]]

[[Category:Wikipedia medicine articles ready to translate]]

[[Category:Czech inventions]]