Etravirine

Drugbox
IUPAC_name = 4- [6-Amino-5-bromo-2- [(4-cyanophenyl)amino] pyrimidin-4-yl] oxy- 3,5-dimethylbenzonitrile

---

CAS_number =
ATC_prefix = J05
ATC_suffix = AG04
ATC_supplemental = [cite web |url=http://www.whocc.no/atcddd/new_atc_ddd.html#ATCDDD_FINAL |title=ATC/DDD Classification (FINAL): New ATC 5th level codes |date=August 27, 2008 |author=WHO International Working Group for Drug Statistics Methodology |publisher=WHO Collaborating Centre for Drug Statistics Methodology |accessdate=2008-09-05]
PubChem = 193962
DrugBank =
C=20|H=15|Br=1|N=6|O=1
molecular_weight = 435.28 g/mol
bioavailability =
protein_bound = 99.9%
metabolism = Hepatic (CYP3A4, CYP2C9, CYP2C19)
elimination_half-life = 41 hours
excretion = Fecal
pregnancy_AU =
pregnancy_US =
pregnancy_category= B
legal_AU =
legal_CA = Schedule VI
legal_UK =
legal_US = Rx-only
legal_status =
routes_of_administration = oral
licence_EU =Intelence
licence_US =Etravirine

Etravirine (formerly known as TMC-125, brand name Intelence) is a drug used for the treatment of HIV. Etravirine is a non-nucleoside reverse transcriptase inhibitor (NNRTIs). Unlike the currently available agents in the class, resistance to other NNRTIs does not seem to confer resistance to etravirine. [cite journal |author=Stellbrink HJ |title=Antiviral drugs in the treatment of AIDS: what is in the pipeline ? |journal=Eur. J. Med. Res. |volume=12 |issue=9 |pages=483–95 |year=2007 |month=October |pmid=17933730 |doi= |url=] Etravirine is marketed by Tibotec, a subsidiary of Johnson & Johnson. On January 2008, the Food and Drug Administration approved its use for patients with established resistance to other drugs, making it the 30th anti-HIV drug approved in the United States and the first to be approved in 2008. [ [http://ap.google.com/article/ALeqM5iCFQR1SKu681KqBBwrXJg1B6q5PAD8U8MS3G0 FDA Approves HIV Drug Etravirine] , Associated Press, January 18, 2008.] It was also approved for use in Canada on April 1, 2008. [cite press release
title = First New NNRTI in Nearly a Decade to Benefit Canadians with HIV/AIDS
publisher = Janssen-Ortho Inc.
date = 2008-04-01
url = http://www.janssen-ortho.com/JOI/pdf_files/INTELENCE_Press_Release_E.pdf
accessdate = 2008-07-09]

Etravirine is licensed in the United States, Canada and the European Union [cite web |url=http://www.tibotec.com/news/detail.jhtml?itemname=news_48 |publisher=Tibotec |title=Intelence receives marketing authorisation in the European Union for HIV combination therapy |accessdate=2008-08-29 |format=HTML |work=] , and is under regulatory review in Switzerland, Russia and Australia. [cite web |url=http://www.aidsmap.com/en/news/46E8FC38-3BB8-4DDD-9FEC-D6BFD5DD69AA.asp |publisher=Aidsmap |title=Etravirine (TMC125, "Intelence") granted accelerated approval in US |accessdate=2008-01-24 |format= |work=]

Indications and dosage

Etravirine, in combination with other anti-retrovirals, is indicated for the treatment of humanimmunodeficiency virus type 1 (HIV-1) infection in antiretroviral treatment-experienced adult patients, who have evidence of viral replication and HIV-1 strains resistant to a non-nucleoside reverse transcriptase inhibitor (NNRTI) and other antiretroviral agents.

The recommended dose of etravirine is 200 mg (two 100 mg tablets) taken twice daily following a meal. The type of food does not affect the exposure to etravirine. [cite web |url=http://www.fda.gov/cder/foi/label/2008/022187lbl.pdf |title=Intelence prescribing information |accessdate=2008-01-31 |format= |work=]

Mechanism of action

Etravirine is a second-generation non-nucleoside reverse transcriptase inhibitor (NNRTI), designed to be active against HIV with mutations that confer resistance to the two most commonly prescribed first-generation NNRTI's, mutation K103N for efavirenz and Y181C for nevirapine.cite web |url=http://www.aidsmeds.com/articles/etravirine_tmc125_hiv_2042_13846.shtml |title=Etravirine—Countdown to Launch |accessdate=2008-02-02 |author=Evans, David |authorlink= |coauthors= |date=2008-01-15 |format= |work= |publisher=AIDSmeds.com |pages= |language= |archiveurl= |archivedate= |quote=] This potency appears to be related to etravirine's flexibility as a molecule. Etravirine is a diarylpyrimidine (DAPY), a type organic molecule with some conformational isomerism that can bind the enzyme reverse transcriptase in multiple conformations, allowing for a more robust interaction between etravirine and the enzyme, even in the presence of mutations.cite journal |author=Das K, Clark AD, Lewi PJ, Heeres J, De Jonge MR, Koymans LM, Vinkers HM, Daeyaert F, Ludovici DW, Kukla MJ, De Corte B, Kavash RW, Ho CY, Ye H, Lichtenstein MA, Andries K, Pauwels R, De Béthune MP, Boyer PL, Clark P, Hughes SH, Janssen PA, Arnold E |title=Roles of conformational and positional adaptability in structure-based design of TMC125-R165335 (etravirine) and related non-nucleoside reverse transcriptase inhibitors that are highly potent and effective against wild-type and drug-resistant HIV-1 variants |journal=J. Med. Chem. |volume=47 |issue=10 |pages=2550–60 |year=2004 |pmid=15115397 |doi=10.1021/jm030558s |issn=] Other diarylpyrimidine-analogues are currently being developed as potential anti-HIV agents, notably rilpivirine.

External links

* [http://www.intelence-info.com/intelence/ Manufacturer's site]
* [http://www.intelence-info.com/intelence/assets/pdf/TMC125_20080118_USPI_USPPI_v1_0.pdf Prescribing information]
* [http://www.aidsmap.com/cms1256807.asp AIDS map]
* [http://www.aidsmeds.com/archive/etravirine_1618.shtml AIDS meds]

References