Tenofovir alafenamide (TAF) as the successor of tenofovir disoproxil fumarate (TDF)

详细信息    查看全文

• 作者：Erik De Clercq ^{erik.declercq@kuleuven.be" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Tenofovir [(R)-PMPA] (PubChem CID ; 464205) ; Tenofovir disoproxil fumarate (TDF) ; Viread® ; (PubChem CID ; 6398764) ; Emtricitabine [(&minus ; )FTC] ; Emtriva® ; (PubChem CID ; 60877) ; Efavirenz ; Sustiva® ; (PubChem CID ; 64139) ; Rilpivirine ; Edurant® ; (PubChem CID ; 6451164) ; Elvitegravir (PubChem CID ; 5277135) ; Cobicistat (PubChem CID ; 25151504) ; Tenofovir alafenamide (TAF) ; GS-7340 (PubChem CID ; 9574768) ; Darunavir ; Prezista® ; (PubChem CID ; 213039)
• 刊名：Biochemical Pharmacology
• 出版年：2016
• 出版时间：1 November 2016
• 年：2016
• 卷：119
• 期：Complete
• 页码：1-7
• 全文大小：606 K

文摘

Tenofovir alafenamide (TAF) can be considered a new prodrug of tenofovir (TFV), as successor of tenofovir disoproxil fumarate (TDF). It is in vivo as potent against human immunodeficiency virus (HIV) at a 30-fold lower dose (10 mg) than TDF (300 mg). TAF has been approved in November 2015 (in the US and EU), as a single-tablet regimen (STR) containing 150 mg elvitegravir (E), 150 mg cobicistat (C), 200 mg emtricitabine [(−)FTC] (F) and 10 mg TAF, marketed as Genvoya®, on 01 March 2016 in the US as an STR containing 25 mg rilpivirine (R), 200 mg F and 25 mg TAF, marketed as Odefsey®, and on 4 April 2016 in the US, as an STR containing 200 mg F and 25 mg TAF, marketed as Descovy®, for the treatment of HIV infections. STR combinations containing TAF and emtricitabine could be paired with a range of third agents, for example, darunavir and cobicistat. TAF has a much lower risk of kidney toxicity or bone density changes than TDF, and also offers long-term potential in the pre-exposure prophylaxis (PrEP) of HIV infections. TAF is specifically accumulated in lymphatic tissue, and in the liver, and hence also holds great potential for the treatment of hepatitis B virus (HBV) infections. Akin to TDF, TAF is converted intracellularly to TFV. Its active diphosphate metabolite (TFVpp) is targeted at the RNA-dependent DNA polymerase (reverse transcriptase) of either HIV or HBV.