Tenofovir alafenamide 25mg tablets
Prescription only
Requires a prescription from a doctor or prescriber
Tablet
25mg
Oral
Active ingredients:
Tenofovir alafenamide
No active safety alerts
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MHRA alerts for Tenofovir alafenamide
Source: MHRA Products DatabaseOGL 3.0
Updated 16 Jan 2026Safety monitoring data
Yellow Card reports
MHRA
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Suspected adverse reactions reported for Tenofovir alafenamide
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Suspected adverse reactions reported for Tenofovir alafenamide
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Vemlidy 25mg tablets
WHO defined daily dose (DDD)
25 mg
Not a recommended dose. The DDD is the assumed average maintenance dose per day for a drug used for its main indication in adults. It is a statistical measure used for research and comparison purposes only.
Source: WHO Collaborating Centre for Drug Statistics Methodology, distributed via the NHS dm+d supplementary mapping files (NHSBSA). Contains public sector information licensed under the Open Government Licence v3.0.
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Similarity is based on WHO Anatomical Therapeutic Chemical (ATC) classification and on a factual NHS dm+d therapeutic-grouping code prefix. Source data: NHS dm+d via TRUD (OGL v3.0), WHO ATC/DDD Index.
NHS prescribing volume and spending trends
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Guidelines from the National Institute for Health and Care Excellence
NICE clinical guidance(3)
Tenofovir alafenamide for treating chronic hepatitis B (terminated appraisal) (TA435)
TA435
Technology appraisal
Updated Mar 2017Cabotegravir with rilpivirine for treating HIV-1 (TA757)
TA757
Technology appraisal
Updated Jan 2022Cabotegravir for preventing HIV-1 in adults and young people (TA1106)
TA1106
Technology appraisal
Updated Nov 2025Source: National Institute for Health and Care Excellence (NICE). Contains public sector information licensed under the Open Government Licence v3.0.
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Codes for healthcare professionals and prescribing systems
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NHS UK identifiers
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SNOMED CT and dm+d codes from NHS TRUD (Technology Reference data Update Distribution), licensed under the Open Government Licence v3.0. ATC codes from the WHO Collaborating Centre for Drug Statistics Methodology (whocc.no).
Active and completed clinical studies from ClinicalTrials.gov
Searching UK clinical trials...
Source: ClinicalTrials.gov, a database of the U.S. National Library of Medicine (NLM), National Institutes of Health (NIH). Data accessed via ClinicalTrials.gov API v2. Trial information is provided for research purposes and does not constitute medical advice.
Academic studies and reviews for this medicine's active substance
Showing the 50 most relevant studies.
Reviews & meta-analyses: 17 · Randomised trials: 31 · 2016–2026
Showing the 50 most relevant studies, sorted by most relevant.
Tenofovir alafenamide versus tenofovir disoproxil fumarate for the treatment of patients with HBeAg-negative chronic hepatitis B virus infection: a randomised, double-blind, phase 3, non-inferiority trial (opens in a new tab)
Marı́a Buti, Edward Gane, Wai Kay Seto, et al.
The Lancet. Gastroenterology & hepatology, 2016
Randomised trial
Highly cited for its field
Cited by 552- Tenofovir
- Adenine
- Alanine
Emtricitabine and tenofovir alafenamide vs emtricitabine and tenofovir disoproxil fumarate for HIV pre-exposure prophylaxis (DISCOVER): primary results from a randomised, double-blind, multicentre, active-controlled, phase 3, non-inferiority trial (opens in a new tab)
Kenneth H. Mayer, Jean‐Michel Molina, Melanie Thompson, et al.
The Lancet, 2020
Randomised trial
Highly cited for its field
Cited by 428- Emtricitabine
- Tenofovir
- Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination
Coformulated bictegravir, emtricitabine, and tenofovir alafenamide versus dolutegravir with emtricitabine and tenofovir alafenamide, for initial treatment of HIV-1 infection (GS-US-380–1490): a randomised, double-blind, multicentre, phase 3, non-inferiority trial (opens in a new tab)
Paul E. Sax, Anton Pozniak, Marisa Montes, et al.
The Lancet, 2017
Randomised trial
Highly cited for its field
Cited by 399- Emtricitabine
- Tenofovir
- Dolutegravir
Bictegravir, emtricitabine, and tenofovir alafenamide versus dolutegravir, abacavir, and lamivudine for initial treatment of HIV-1 infection (GS-US-380-1489): a double-blind, multicentre, phase 3, randomised controlled non-inferiority trial (opens in a new tab)
Joel E. Gallant, Adriano Lazzarin, Anthony Mills, et al.
The Lancet, 2017
Randomised trial
Highly cited for its field
Cited by 385- Emtricitabine
- Tenofovir
- Dolutegravir
Dolutegravir with emtricitabine and tenofovir alafenamide or tenofovir disoproxil fumarate versus efavirenz, emtricitabine, and tenofovir disoproxil fumarate for initial treatment of HIV-1 infection (ADVANCE): week 96 results from a randomised, phase 3, non-inferiority trial (opens in a new tab)
François Venter, Simiso Sokhela, Bryony Simmons, et al.
The Lancet HIV, 2020
Randomised trial
Highly cited for its field
Cited by 264- Emtricitabine
- Tenofovir
- Duration of Therapy
Switching to fixed-dose bictegravir, emtricitabine, and tenofovir alafenamide from dolutegravir plus abacavir and lamivudine in virologically suppressed adults with HIV-1: 48 week results of a randomised, double-blind, multicentre, active-controlled, phase 3, non-inferiority trial (opens in a new tab)
Jean‐Michel Molina, Douglas Ward, Indira Brar, et al.
The Lancet HIV, 2018
Randomised trial
Highly cited for its field
Cited by 204- Emtricitabine
- Tenofovir
- Sustained Virologic Response
Efficacy and safety of switching to fixed-dose bictegravir, emtricitabine, and tenofovir alafenamide from boosted protease inhibitor-based regimens in virologically suppressed adults with HIV-1: 48 week results of a randomised, open-label, multicentre, phase 3, non-inferiority trial (opens in a new tab)
Eric S. Daar, Edwin DeJesus, Peter Ruane, et al.
The Lancet HIV, 2018
Randomised trial
Highly cited for its field
Cited by 180- Emtricitabine
- Tenofovir
- Sustained Virologic Response
Bictegravir combined with emtricitabine and tenofovir alafenamide versus dolutegravir, abacavir, and lamivudine for initial treatment of HIV-1 infection: week 96 results from a randomised, double-blind, multicentre, phase 3, non-inferiority trial (opens in a new tab)
David A. Wohl, Yazdan Yazdanpanah, Axel Baumgarten, et al.
The Lancet HIV, 2019
Randomised trial
Highly cited for its field
Cited by 166- Tenofovir
- Dolutegravir
- Abacavir
Efficacy and safety of tenofovir alafenamide versus tenofovir disoproxil fumarate given as fixed-dose combinations containing emtricitabine as backbones for treatment of HIV-1 infection in virologically suppressed adults: a randomised, double-blind, active-controlled phase 3 trial (opens in a new tab)
Joel E. Gallant, Eric S. Daar, François Raffi, et al.
The Lancet HIV, 2016
Randomised trial
Highly cited for its field
Cited by 165- Emtricitabine
- Tenofovir
- Adenine
Efficacy and safety of dolutegravir with emtricitabine and tenofovir alafenamide fumarate or tenofovir disoproxil fumarate, and efavirenz, emtricitabine, and tenofovir disoproxil fumarate HIV antiretroviral therapy regimens started in pregnancy (IMPAACT 2010/VESTED): a multicentre, open-label, randomised, controlled, phase 3 trial (opens in a new tab)
Shahin Lockman, Sean S. Brummel, Lauren Ziemba, et al.
The Lancet, 2021
Randomised trial
Highly cited for its field
Cited by 163- Emtricitabine
- Tenofovir
- Dolutegravir
Sources: aggregated from Europe PMC (EMBL-EBI), OpenAlex, Crossref, PubMed and other open scholarly databases. Retracted articles are excluded. Study information is provided for research purposes and does not constitute medical advice.
Pharmacology and chemical data from DrugBank
Key facts
Drug status
Approved
Major interactions
13 found
Half-life
0.51 hours
Mechanism
Tenofovir alafenamide presents 91% lower plasma concentration with an intracellu…
Food interactions
3 warnings
Human targets
None mapped
Data: DrugBank · CC BY-NC 4.0
Pharmacokinetics at a glance
Absorption
16 ng/ml
As compared to the parent molecule, [tenofovir], tenofovir alafenamide presents a lipophilic group that masks the negative charge of the parent moiety which improves its oral bioavailability.
[A178060]
Tenofovir…
[A178060]
Tenofovir…
Half-life
0.51 hours
The reported half-life for tenofovir alafenamide is of 0.51 hours.
[A178231]
[A178231]
Protein binding
80%
Tenofovir alafenamide is reported to bind to plasma proteins and ex vivo studies have registered that approximately 80% of the administered dose of this drug is presented in a bound state.
[A178231]
…
[A178231]
…
Volume of distribution
100 L
In clinical trials, the reported volume of distribution of tenofovir alafenamide was higher than 100 L.
[A178438]
[A178438]
Metabolism
1-2 days
To be activated, tenofovir alafenamide is required to be hydrolyzed to the parent compound [tenofovir] by the activity of cathepsin A or carboxylesterase 1.…
Elimination
47%
Tenofovir alafenamide has been registered to present a bile elimination that corresponds to 47% of the administered dose and a renal elimination the represents about 36%.…
Clearance
117 L/h
The reported clearance rate of tenofovir alafenamide is 117 L/h.…
Pharmacokinetic data: DrugBank · CC BY-NC 4.0
Status:
Approved
Investigational
Small molecule
About this compound
Tenofovir alafenamide is a novel [tenofovir] prodrug developed in order to improve renal safety when compared to the counterpart [tenofovir disoproxil].[A178060] Both of these prodrugs were first created to cover the polar phosphonic acid group on tenofovir by using a novel oxycarbonyloxymethyl linkers to improve the oral bioavailability and intestinal diffusion.[T239] Tenofovir alafenamide is an alanine ester form characterized for presenting low systemic levels but high intracellular concentration.[A178219] It has been reported to produce a large antiviral efficacy at doses ten times lower than tenofovir disoproxil.[A178327] Tenofovir alafenamide is indicated to treat chronic hepatitis B,[L6241] treat HIV-1,[L4388][L6277][L6280][L6283] and prevent HIV-1 infections.[L4388][L9010]
Tenofovir alafenamide was developed by Gilead Sciences Inc and granted FDA approval on 5 November 2015.[L6271]
Tenofovir alafenamide was developed by Gilead Sciences Inc and granted FDA approval on 5 November 2015.[L6271]
Properties:
View FDA drug labelsolid
Avg. mass: 476.47 Da
DrugBank indication
Tenofovir alafenamide is indicated for the treatment of hepatitis B virus infection in adults and pediatric patients 12 years of age and older with compensated liver disease.
[L43582]
In combination with [emtricitabine] and other antiretrovirals, it is indicated for the treatment of HIV-1 infection in adolescent and adult patients with a weight higher than 35 kg.
[L4388]
This combination is also indicated to prevent HIV-1 infections in high-risk adolescent and adult patients, excluding patients at risk from receptive vaginal sex.
[L4388][L9010]
When combined with antiretrovirals other than protease inhibitors that require a CYP3A inhibitor, it can be used to treat pediatric patients weighing 25-35 kg.
[L4388]
In the combination product with emtricitabine and [bictegravir], tenofovir alafenamide is considered a complete treatment regimen for HIV-1 infections for treatment-naive patients or patients virologically suppressed for at least three months with no history of treatment failure.
[L6277][L38944][L44226]
This combination product is also used to replace the current antiretroviral regimen in those who are virologically-suppressed (HIV-1 RNA less than 50 copies per mL) on a stable antiretroviral regimen with no known or suspected substitutions associated with resistance to bictegravir or tenofovir.
[L50522][L53758]
Additionally, the combination product including [elvitegravir], [cobicistat], emtricitabine and tenofovir alafenamide and the combination product including emtricitabine, [rilpivirine] and tenofovir alafenamide can be used in the treatment of HIV-1 infection in patients older than 12 years with no previous antiretroviral therapy history or who are virologically suppressed for at least 6 months with no history of treatment failure.
[L6280]
The combination product including [darunavir], cobicistat, emtricitabine, and tenofovir alafenamide is indicated for the treatment of HIV-1 infection in adults without prior antiretroviral therapy or in patients virologically suppressed for 6 months and no reported resistance to darunavir or tenofovir.
[L6283]
[L43582]
In combination with [emtricitabine] and other antiretrovirals, it is indicated for the treatment of HIV-1 infection in adolescent and adult patients with a weight higher than 35 kg.
[L4388]
This combination is also indicated to prevent HIV-1 infections in high-risk adolescent and adult patients, excluding patients at risk from receptive vaginal sex.
[L4388][L9010]
When combined with antiretrovirals other than protease inhibitors that require a CYP3A inhibitor, it can be used to treat pediatric patients weighing 25-35 kg.
[L4388]
In the combination product with emtricitabine and [bictegravir], tenofovir alafenamide is considered a complete treatment regimen for HIV-1 infections for treatment-naive patients or patients virologically suppressed for at least three months with no history of treatment failure.
[L6277][L38944][L44226]
This combination product is also used to replace the current antiretroviral regimen in those who are virologically-suppressed (HIV-1 RNA less than 50 copies per mL) on a stable antiretroviral regimen with no known or suspected substitutions associated with resistance to bictegravir or tenofovir.
[L50522][L53758]
Additionally, the combination product including [elvitegravir], [cobicistat], emtricitabine and tenofovir alafenamide and the combination product including emtricitabine, [rilpivirine] and tenofovir alafenamide can be used in the treatment of HIV-1 infection in patients older than 12 years with no previous antiretroviral therapy history or who are virologically suppressed for at least 6 months with no history of treatment failure.
[L6280]
The combination product including [darunavir], cobicistat, emtricitabine, and tenofovir alafenamide is indicated for the treatment of HIV-1 infection in adults without prior antiretroviral therapy or in patients virologically suppressed for 6 months and no reported resistance to darunavir or tenofovir.
[L6283]
Also known as(138)
Tenofovir alafenamide
Pr160Gag-Pol
2.7.7.7
3.4.16.5
Carboxypeptidase C
Carboxypeptidase L
Cathepsin A
PPCA
Molecular properties(19)
Drug interactions(1336)
Known interactions with other medicines. Always consult a healthcare professional.
The serum concentration of Tenofovir alafenamide can be decreased when it is combined with Phenytoin.
Fosphenytoin
Moderate
The serum concentration of Tenofovir alafenamide can be decreased when it is combined with Fosphenytoin.
Atazanavir
Moderate
The serum concentration of Atazanavir can be decreased when it is combined with Tenofovir alafenamide.
Didanosine
Moderate
The serum concentration of Didanosine can be increased when it is combined with Tenofovir alafenamide.
Simeprevir
Moderate
The serum concentration of Tenofovir alafenamide can be increased when it is combined with Simeprevir.
Telaprevir
Moderate
The serum concentration of Tenofovir alafenamide can be increased when it is combined with Telaprevir.
Tipranavir
Moderate
The serum concentration of Tenofovir alafenamide can be decreased when it is combined with Tipranavir.
Taxifolin may decrease the excretion rate of Tenofovir alafenamide which could result in a higher serum level.
Licofelone
Moderate
Licofelone may decrease the excretion rate of Tenofovir alafenamide which could result in a higher serum level.
Polmacoxib
Moderate
Polmacoxib may decrease the excretion rate of Tenofovir alafenamide which could result in a higher serum level.
Ebselen may decrease the excretion rate of Tenofovir alafenamide which could result in a higher serum level.
Flurbiprofen axetil
Moderate
Flurbiprofen axetil may decrease the excretion rate of Tenofovir alafenamide which could result in a higher serum level.
The risk or severity of nephrotoxicity can be increased when Tenofovir alafenamide is combined with Foscarnet.
The serum concentration of Tenofovir alafenamide can be increased when it is combined with Mannitol.
Icosapent may increase the nephrotoxic activities of Tenofovir alafenamide.
Cefotiam may increase the nephrotoxic activities of Tenofovir alafenamide.
Mesalazine
Major
The risk or severity of nephrotoxicity can be increased when Mesalazine is combined with Tenofovir alafenamide.
Cefmenoxime
Moderate
Cefmenoxime may increase the nephrotoxic activities of Tenofovir alafenamide.
Cefmetazole
Moderate
Cefmetazole may increase the nephrotoxic activities of Tenofovir alafenamide.
Pamidronic acid
Moderate
Pamidronic acid may increase the nephrotoxic activities of Tenofovir alafenamide.
Tenofovir disoproxil
Moderate
The serum concentration of Tenofovir alafenamide can be increased when it is combined with Tenofovir disoproxil.
Indomethacin
Moderate
Indomethacin may increase the nephrotoxic activities of Tenofovir alafenamide.
The serum concentration of Tenofovir alafenamide can be increased when it is combined with Cidofovir.
Triamterene
Moderate
Triamterene may increase the nephrotoxic activities of Tenofovir alafenamide.
Cefpiramide
Moderate
Cefpiramide may increase the nephrotoxic activities of Tenofovir alafenamide.
Ceftazidime
Moderate
The serum concentration of Tenofovir alafenamide can be increased when it is combined with Ceftazidime.
Loracarbef
Moderate
Loracarbef may increase the nephrotoxic activities of Tenofovir alafenamide.
Framycetin
Moderate
Framycetin may increase the nephrotoxic activities of Tenofovir alafenamide.
Cefalotin may increase the nephrotoxic activities of Tenofovir alafenamide.
Nabumetone
Moderate
Nabumetone may increase the nephrotoxic activities of Tenofovir alafenamide.
Ketorolac may increase the nephrotoxic activities of Tenofovir alafenamide.
Tenoxicam may increase the nephrotoxic activities of Tenofovir alafenamide.
Amikacin may increase the nephrotoxic activities of Tenofovir alafenamide.
Celecoxib may increase the nephrotoxic activities of Tenofovir alafenamide.
Cefotaxime
Moderate
Cefotaxime may increase the nephrotoxic activities of Tenofovir alafenamide.
Tolmetin may increase the nephrotoxic activities of Tenofovir alafenamide.
Rofecoxib may increase the nephrotoxic activities of Tenofovir alafenamide.
The serum concentration of Tenofovir alafenamide can be increased when it is combined with Piroxicam.
Methotrexate
Moderate
The serum concentration of Tenofovir alafenamide can be increased when it is combined with Methotrexate.
Cephalexin
Moderate
The serum concentration of Tenofovir alafenamide can be increased when it is combined with Cephalexin.
Fenoprofen
Moderate
Fenoprofen may increase the nephrotoxic activities of Tenofovir alafenamide.
Valaciclovir
Moderate
The serum concentration of Tenofovir alafenamide can be increased when it is combined with Valaciclovir.
Valdecoxib
Moderate
Valdecoxib may increase the nephrotoxic activities of Tenofovir alafenamide.
Diclofenac
Moderate
Diclofenac may increase the nephrotoxic activities of Tenofovir alafenamide.
Sulindac may increase the nephrotoxic activities of Tenofovir alafenamide.
Bacitracin
Moderate
Bacitracin may increase the nephrotoxic activities of Tenofovir alafenamide.
Amphotericin B
Moderate
Amphotericin B may increase the nephrotoxic activities of Tenofovir alafenamide.
Tobramycin
Moderate
The serum concentration of Tenofovir alafenamide can be increased when it is combined with Tobramycin.
Cephaloglycin
Moderate
Cephaloglycin may increase the nephrotoxic activities of Tenofovir alafenamide.
Furosemide
Moderate
The serum concentration of Tenofovir alafenamide can be increased when it is combined with Furosemide.
Showing 50 of 1336 interactions
Food & lifestyle interactions
Advice
Avoid St. John's Wort. St. John's Wort can cause drug interaction and decrease the serum concentration of tenofovir alafenamide.
Advice
Take at the same time every day.
Advice
Take with or without food. Recommendations vary from product to product - consult individual product monographs for additional information.
Toxicity & overdose
The LD50 of tenofovir alafenamide has not been reported. In cases of overdose, continuous monitoring of vital signs is required as the adverse effects in high doses has not been evaluated. However, in case of overdose, tenofovir is efficiently removed by hemodialysis with an extraction coefficient of 54%.
[L6286]
Carcinogenic reports have only been performed with [tenofovir disoproxil] and it is important to consider that tenofovir alafenamide does not present a high systemic exposure.
However, long-term exposure with 10-fold dosages of tenofovir disoproxil was reported to produce liver adenomas in females. Tenofovir alafenamide was not reported to present mutagenic potential and it did not present effects on fertility.
[L6286]
[L6286]
Carcinogenic reports have only been performed with [tenofovir disoproxil] and it is important to consider that tenofovir alafenamide does not present a high systemic exposure.
However, long-term exposure with 10-fold dosages of tenofovir disoproxil was reported to produce liver adenomas in females. Tenofovir alafenamide was not reported to present mutagenic potential and it did not present effects on fertility.
[L6286]
How it works
Mechanism of action
Tenofovir alafenamide presents 91% lower plasma concentration with an intracellular presence of about 20-fold higher when compared to [tenofovir disoproxil].[A178219] This is due to its prolonged systemic exposure and its higher intracellular accumulation of the active metabolite tenofovir diphosphate.[A18473]
Tenofovir alafenamide accumulates more in peripheral blood mononuclear cells compared to red blood cells.[A18473]
Once activated, tenofovir acts with different mechanisms including the inhibition of viral polymerase, causing chain termination and the inhibition of viral synthesis.[L6241] To know more about the specific mechanism of action of the active form, please visit the drug entry of [tenofovir].
Tenofovir alafenamide accumulates more in peripheral blood mononuclear cells compared to red blood cells.[A18473]
Once activated, tenofovir acts with different mechanisms including the inhibition of viral polymerase, causing chain termination and the inhibition of viral synthesis.[L6241] To know more about the specific mechanism of action of the active form, please visit the drug entry of [tenofovir].
Pharmacodynamics
Tenofovir alafenamide has been shown to be a potent inhibitor of hepatitis B viral replication.[A178249]
Tenofovir alafenamide presents a better renal tolerance when compared with the counterpart [tenofovir disoproxil]. This improved safety profile seems to be related to a lower plasma concentration of tenofovir.[A178060]
In clinical trials, tenofovir alafenamide was shown to present 5-fold more potent antiviral activity against HIV-1 when compared to tenofovir disoproxil.[A178060]
Tenofovir alafenamide presents a better renal tolerance when compared with the counterpart [tenofovir disoproxil]. This improved safety profile seems to be related to a lower plasma concentration of tenofovir.[A178060]
In clinical trials, tenofovir alafenamide was shown to present 5-fold more potent antiviral activity against HIV-1 when compared to tenofovir disoproxil.[A178060]
Pharmacokinetics
How the body processes this drug — absorption, distribution, metabolism, and elimination
Absorption
As compared to the parent molecule, [tenofovir], tenofovir alafenamide presents a lipophilic group that masks the negative charge of the parent moiety which improves its oral bioavailability.
[A178060]
Tenofovir alafenamide is highly stable in plasma and, after administration of this prodrug, there is a low concentration of tenofovir in plasma. After oral administration, tenofovir alafenamide is rapidly absorbed by the gut. When a single dose is administered, a peak concentration of 16 ng/ml of the parent compound, corresponding to about 73% of the dose, is observed after 2 hours with an AUC of 270 ng\*h/mL.
[A178060][A18473]
Once inside the body, tenofovir alafenamide enters hepatocytes by passive diffusion regulated by the organic anion transporters 1B1 and 1B3 for its activation.
[A178249]
Administration of tenofovir alafenamide concomitantly with a high-fat meal results in an increase of about 65% in its internal exposure.
[L6286]
[A178060]
Tenofovir alafenamide is highly stable in plasma and, after administration of this prodrug, there is a low concentration of tenofovir in plasma. After oral administration, tenofovir alafenamide is rapidly absorbed by the gut. When a single dose is administered, a peak concentration of 16 ng/ml of the parent compound, corresponding to about 73% of the dose, is observed after 2 hours with an AUC of 270 ng\*h/mL.
[A178060][A18473]
Once inside the body, tenofovir alafenamide enters hepatocytes by passive diffusion regulated by the organic anion transporters 1B1 and 1B3 for its activation.
[A178249]
Administration of tenofovir alafenamide concomitantly with a high-fat meal results in an increase of about 65% in its internal exposure.
[L6286]
Half-life
The reported half-life for tenofovir alafenamide is of 0.51 hours.
[A178231]
[A178231]
Protein binding
Tenofovir alafenamide is reported to bind to plasma proteins and ex vivo studies have registered that approximately 80% of the administered dose of this drug is presented in a bound state.
[A178231]
[A178231]
Volume of distribution
In clinical trials, the reported volume of distribution of tenofovir alafenamide was higher than 100 L.
[A178438]
[A178438]
Metabolism
To be activated, tenofovir alafenamide is required to be hydrolyzed to the parent compound [tenofovir] by the activity of cathepsin A or carboxylesterase 1. Tenofovir alafenamide presents significant plasma stability and hence, its activation is performed inside the target cells.
[A178060]
After activation, tenofovir is further processed and after 1-2 days, it is detected in plasma almost completely transformed to uric acid.
[A178060]
[A178060]
After activation, tenofovir is further processed and after 1-2 days, it is detected in plasma almost completely transformed to uric acid.
[A178060]
Route of elimination
Tenofovir alafenamide has been registered to present a bile elimination that corresponds to 47% of the administered dose and a renal elimination the represents about 36%. From the recovered dose in urine, about 75% is represented as unchanged [tenofovir] followed by uric acid and a small dose of tenofovir alafenamide. On the other hand, in feces, 99% of the recovered dose corresponds to tenofovir.
[A178060]
[A178060]
Clearance
The reported clearance rate of tenofovir alafenamide is 117 L/h. In patients with severe renal impairment, this value can be decreased by 50%, reporting a rate of 61.7 L/h.
[L6337]
[L6337]
Metabolizing enzymes(7)
Enzymes involved in drug metabolism — important for understanding drug interactions
Enzyme activity key
substrate
inhibitor
inducer
CTSALysosomal protective protein
substrate
CES1Liver carboxylesterase 1
substrate
CYP3A4Cytochrome P450 3A4
substrate
AK1Adenylate kinase isoenzyme 1
substrate
AK2Adenylate kinase 2, mitochondrial
substrate
NME1Nucleoside diphosphate kinase A
substrate
NME2Nucleoside diphosphate kinase B
substrate
Transporters(7)
Proteins that transport this drug across cell membranes
ATP-dependent translocase ABCB1
ABCB1
substrate
Specific functionABC-type xenobiotic transporter activity
Cellular location
Cell membrane
General function & pharmacology
Translocates drugs and phospholipids across the membrane .
PMID:2897240 PMID:35970996 PMID:8898203 PMID:9038218 PMID:35507548
Catalyzes the flop of phospholipids from the cytoplasmic to the exoplasmic leaflet of the apical membrane. Participates mainly to the flop of phosphatidylcholine, phosphatidylethanolamine, beta-D-glucosylceramides and sphingomyelins .
PMID:8898203
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells PMID:2897240 PMID:35970996 PMID:9038218
PMID:2897240 PMID:35970996 PMID:8898203 PMID:9038218 PMID:35507548
Catalyzes the flop of phospholipids from the cytoplasmic to the exoplasmic leaflet of the apical membrane. Participates mainly to the flop of phosphatidylcholine, phosphatidylethanolamine, beta-D-glucosylceramides and sphingomyelins .
PMID:8898203
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells PMID:2897240 PMID:35970996 PMID:9038218
ATP-binding cassette sub-family C member 4
ABCC4
substrate
Specific function15-hydroxyprostaglandin dehydrogenase (NAD+) activity
Cellular location
Basolateral cell membrane
General function & pharmacology
ATP-dependent transporter of the ATP-binding cassette (ABC) family that actively extrudes physiological compounds and xenobiotics from cells. Transports a range of endogenous molecules that have a key role in cellular communication and signaling, including cyclic nucleotides such as cyclic AMP (cAMP) and cyclic GMP (cGMP), bile acids, steroid conjugates, urate, and prostaglandins .
PMID:11856762 PMID:12523936 PMID:12835412 PMID:12883481 PMID:15364914 PMID:15454390 PMID:16282361 PMID:17959747 PMID:18300232 PMID:26721430
Mediates the ATP-dependent efflux of glutathione conjugates such as leukotriene C4 (LTC4) and leukotriene B4 (LTB4) too. The presence of GSH is necessary for the ATP-dependent transport of LTB4, whereas GSH is not required for the transport of LTC4 .
PMID:17959747
Mediates the cotransport of bile acids with reduced glutathione (GSH) .
PMID:12523936 PMID:12883481 PMID:16282361
Transports a wide range of drugs and their metabolites, including anticancer, antiviral and antibiotics molecules .
PMID:11856762 PMID:12105214 PMID:15454390 PMID:17344354 PMID:18300232
Confers resistance to anticancer agents such as methotrexate PMID:11106685
PMID:11856762 PMID:12523936 PMID:12835412 PMID:12883481 PMID:15364914 PMID:15454390 PMID:16282361 PMID:17959747 PMID:18300232 PMID:26721430
Mediates the ATP-dependent efflux of glutathione conjugates such as leukotriene C4 (LTC4) and leukotriene B4 (LTB4) too. The presence of GSH is necessary for the ATP-dependent transport of LTB4, whereas GSH is not required for the transport of LTC4 .
PMID:17959747
Mediates the cotransport of bile acids with reduced glutathione (GSH) .
PMID:12523936 PMID:12883481 PMID:16282361
Transports a wide range of drugs and their metabolites, including anticancer, antiviral and antibiotics molecules .
PMID:11856762 PMID:12105214 PMID:15454390 PMID:17344354 PMID:18300232
Confers resistance to anticancer agents such as methotrexate PMID:11106685
Solute carrier family 22 member 6
SLC22A6
substrate
Specific functionalpha-ketoglutarate transmembrane transporter activity
Cellular location
Basolateral cell membrane
General function & pharmacology
Secondary active transporter that functions as a Na(+)-independent organic anion (OA)/dicarboxylate antiporter where the uptake of one molecule of OA into the cell is coupled with an efflux of one molecule of intracellular dicarboxylate such as 2-oxoglutarate or glutarate .
PMID:11669456 PMID:11907186 PMID:14675047 PMID:22108572 PMID:23832370 PMID:28534121 PMID:9950961
Mediates the uptake of OA across the basolateral side of proximal tubule epithelial cells, thereby contributing to the renal elimination of endogenous OA from the systemic circulation into the urine .
PMID:9887087
Functions as a biopterin transporters involved in the uptake and the secretion of coenzymes tetrahydrobiopterin (BH4), dihydrobiopterin (BH2) and sepiapterin to urine, thereby determining baseline levels of blood biopterins .
PMID:28534121
Transports prostaglandin E2 (PGE2) and prostaglandin F2-alpha (PGF2-alpha) and may contribute to their renal excretion .
PMID:11907186
Also mediates the uptake of cyclic nucleotides such as cAMP and cGMP .
PMID:26377792
Involved in the transport of neuroactive tryptophan metabolites kynurenate (KYNA) and xanthurenate (XA) and may contribute to their secretion from the brain .
PMID:22108572 PMID:23832370
May transport glutamate .
PMID:26377792
Also involved in the disposition of uremic toxins and potentially toxic xenobiotics by the renal organic anion secretory pathway, helping reduce their undesired toxicological effects on the body .
PMID:11669456 PMID:14675047
Uremic toxins include the indoxyl sulfate (IS), hippurate/N-benzoylglycine (HA), indole acetate (IA), 3-carboxy-4- methyl-5-propyl-2-furanpropionate (CMPF) and urate .
PMID:14675047 PMID:26377792
Xenobiotics include the mycotoxin ochratoxin (OTA) .
PMID:11669456
May also contribute to the transport of organic compounds in testes across the blood-testis-barrier PMID:35307651
PMID:11669456 PMID:11907186 PMID:14675047 PMID:22108572 PMID:23832370 PMID:28534121 PMID:9950961
Mediates the uptake of OA across the basolateral side of proximal tubule epithelial cells, thereby contributing to the renal elimination of endogenous OA from the systemic circulation into the urine .
PMID:9887087
Functions as a biopterin transporters involved in the uptake and the secretion of coenzymes tetrahydrobiopterin (BH4), dihydrobiopterin (BH2) and sepiapterin to urine, thereby determining baseline levels of blood biopterins .
PMID:28534121
Transports prostaglandin E2 (PGE2) and prostaglandin F2-alpha (PGF2-alpha) and may contribute to their renal excretion .
PMID:11907186
Also mediates the uptake of cyclic nucleotides such as cAMP and cGMP .
PMID:26377792
Involved in the transport of neuroactive tryptophan metabolites kynurenate (KYNA) and xanthurenate (XA) and may contribute to their secretion from the brain .
PMID:22108572 PMID:23832370
May transport glutamate .
PMID:26377792
Also involved in the disposition of uremic toxins and potentially toxic xenobiotics by the renal organic anion secretory pathway, helping reduce their undesired toxicological effects on the body .
PMID:11669456 PMID:14675047
Uremic toxins include the indoxyl sulfate (IS), hippurate/N-benzoylglycine (HA), indole acetate (IA), 3-carboxy-4- methyl-5-propyl-2-furanpropionate (CMPF) and urate .
PMID:14675047 PMID:26377792
Xenobiotics include the mycotoxin ochratoxin (OTA) .
PMID:11669456
May also contribute to the transport of organic compounds in testes across the blood-testis-barrier PMID:35307651
Organic anion transporter 3
SLC22A8
substrate
Specific functionorganic anion transmembrane transporter activity
Cellular location
Basolateral cell membrane
General function & pharmacology
Functions as an organic anion/dicarboxylate exchanger that couples organic anion uptake indirectly to the sodium gradient .
PMID:14586168 PMID:15644426 PMID:15846473 PMID:16455804 PMID:31553721
Transports organic anions such as estrone 3-sulfate (E1S) and urate in exchange for dicarboxylates such as glutarate or ketoglutarate (2-oxoglutarate) .
PMID:14586168 PMID:15846473 PMID:15864504 PMID:22108572 PMID:23832370
Plays an important role in the excretion of endogenous and exogenous organic anions, especially from the kidney and the brain .
PMID:11306713 PMID:14586168 PMID:15846473
E1S transport is pH- and chloride-dependent and may also involve E1S/cGMP exchange .
PMID:26377792
Responsible for the transport of prostaglandin E2 (PGE2) and prostaglandin F2(alpha) (PGF2(alpha)) in the basolateral side of the renal tubule .
PMID:11907186
Involved in the transport of neuroactive tryptophan metabolites kynurenate and xanthurenate .
PMID:22108572 PMID:23832370
Functions as a biopterin transporters involved in the uptake and the secretion of coenzymes tetrahydrobiopterin (BH4), dihydrobiopterin (BH2) and sepiapterin to urine, thereby determining baseline levels of blood biopterins .
PMID:28534121
May be involved in the basolateral transport of steviol, a metabolite of the popular sugar substitute stevioside .
PMID:15644426
May participate in the detoxification/ renal excretion of drugs and xenobiotics, such as the histamine H(2)-receptor antagonists fexofenadine and cimetidine, the antibiotic benzylpenicillin (PCG), the anionic herbicide 2,4-dichloro-phenoxyacetate (2,4-D), the diagnostic agent p-aminohippurate (PAH), the antiviral acyclovir (ACV), and the mycotoxin ochratoxin (OTA), by transporting these exogenous organic anions across the cell membrane in exchange for dicarboxylates such as 2-oxoglutarate .
PMID:11669456 PMID:15846473 PMID:16455804
Contributes to the renal uptake of potent uremic toxins (indoxyl sulfate (IS), indole acetate (IA), hippurate/N-benzoylglycine (HA) and 3-carboxy-4-methyl-5-propyl-2-furanpropionate (CMPF)), pravastatin, PCG, E1S and dehydroepiandrosterone sulfate (DHEAS), and is partly involved in the renal uptake of temocaprilat (an angiotensin-converting enzyme (ACE) inhibitor) .
PMID:14675047
May contribute to the release of cortisol in the adrenals .
PMID:15864504
Involved in one of the detoxification systems on the choroid plexus (CP), removes substrates such as E1S or taurocholate (TC), PCG, 2,4-D and PAH, from the cerebrospinal fluid (CSF) to the blood for eventual excretion in urine and bile (By similarity). Also contributes to the uptake of several other organic compounds such as the prostanoids prostaglandin E(2) and prostaglandin F(2-alpha), L-carnitine, and the therapeutic drugs allopurinol, 6-mercaptopurine (6-MP) and 5-fluorouracil (5-FU) (By similarity). Mediates the transport of PAH, PCG, and the statins pravastatin and pitavastatin, from the cerebrum into the blood circulation across the blood-brain barrier (BBB).
In summary, plays a role in the efflux of drugs and xenobiotics, helping reduce their undesired toxicological effects on the body (By similarity)
PMID:14586168 PMID:15644426 PMID:15846473 PMID:16455804 PMID:31553721
Transports organic anions such as estrone 3-sulfate (E1S) and urate in exchange for dicarboxylates such as glutarate or ketoglutarate (2-oxoglutarate) .
PMID:14586168 PMID:15846473 PMID:15864504 PMID:22108572 PMID:23832370
Plays an important role in the excretion of endogenous and exogenous organic anions, especially from the kidney and the brain .
PMID:11306713 PMID:14586168 PMID:15846473
E1S transport is pH- and chloride-dependent and may also involve E1S/cGMP exchange .
PMID:26377792
Responsible for the transport of prostaglandin E2 (PGE2) and prostaglandin F2(alpha) (PGF2(alpha)) in the basolateral side of the renal tubule .
PMID:11907186
Involved in the transport of neuroactive tryptophan metabolites kynurenate and xanthurenate .
PMID:22108572 PMID:23832370
Functions as a biopterin transporters involved in the uptake and the secretion of coenzymes tetrahydrobiopterin (BH4), dihydrobiopterin (BH2) and sepiapterin to urine, thereby determining baseline levels of blood biopterins .
PMID:28534121
May be involved in the basolateral transport of steviol, a metabolite of the popular sugar substitute stevioside .
PMID:15644426
May participate in the detoxification/ renal excretion of drugs and xenobiotics, such as the histamine H(2)-receptor antagonists fexofenadine and cimetidine, the antibiotic benzylpenicillin (PCG), the anionic herbicide 2,4-dichloro-phenoxyacetate (2,4-D), the diagnostic agent p-aminohippurate (PAH), the antiviral acyclovir (ACV), and the mycotoxin ochratoxin (OTA), by transporting these exogenous organic anions across the cell membrane in exchange for dicarboxylates such as 2-oxoglutarate .
PMID:11669456 PMID:15846473 PMID:16455804
Contributes to the renal uptake of potent uremic toxins (indoxyl sulfate (IS), indole acetate (IA), hippurate/N-benzoylglycine (HA) and 3-carboxy-4-methyl-5-propyl-2-furanpropionate (CMPF)), pravastatin, PCG, E1S and dehydroepiandrosterone sulfate (DHEAS), and is partly involved in the renal uptake of temocaprilat (an angiotensin-converting enzyme (ACE) inhibitor) .
PMID:14675047
May contribute to the release of cortisol in the adrenals .
PMID:15864504
Involved in one of the detoxification systems on the choroid plexus (CP), removes substrates such as E1S or taurocholate (TC), PCG, 2,4-D and PAH, from the cerebrospinal fluid (CSF) to the blood for eventual excretion in urine and bile (By similarity). Also contributes to the uptake of several other organic compounds such as the prostanoids prostaglandin E(2) and prostaglandin F(2-alpha), L-carnitine, and the therapeutic drugs allopurinol, 6-mercaptopurine (6-MP) and 5-fluorouracil (5-FU) (By similarity). Mediates the transport of PAH, PCG, and the statins pravastatin and pitavastatin, from the cerebrum into the blood circulation across the blood-brain barrier (BBB).
In summary, plays a role in the efflux of drugs and xenobiotics, helping reduce their undesired toxicological effects on the body (By similarity)
Broad substrate specificity ATP-binding cassette transporter ABCG2
ABCG2
substrate
Specific functionABC-type xenobiotic transporter activity
Cellular location
Cell membrane
General function & pharmacology
Broad substrate specificity ATP-dependent transporter of the ATP-binding cassette (ABC) family that actively extrudes a wide variety of physiological compounds, dietary toxins and xenobiotics from cells .
PMID:11306452 PMID:12958161 PMID:19506252 PMID:20705604 PMID:28554189 PMID:30405239 PMID:31003562
Involved in porphyrin homeostasis, mediating the export of protoporphyrin IX (PPIX) from both mitochondria to cytosol and cytosol to extracellular space, it also functions in the cellular export of heme .
PMID:20705604 PMID:23189181
Also mediates the efflux of sphingosine-1-P from cells .
PMID:20110355
Acts as a urate exporter functioning in both renal and extrarenal urate excretion .
PMID:19506252 PMID:20368174 PMID:22132962 PMID:31003562 PMID:36749388
In kidney, it also functions as a physiological exporter of the uremic toxin indoxyl sulfate (By similarity). Also involved in the excretion of steroids like estrone 3-sulfate/E1S, 3beta-sulfooxy-androst-5-en-17-one/DHEAS, and other sulfate conjugates .
PMID:12682043 PMID:28554189 PMID:30405239
Mediates the secretion of the riboflavin and biotin vitamins into milk (By similarity). Extrudes pheophorbide a, a phototoxic porphyrin catabolite of chlorophyll, reducing its bioavailability (By similarity).
Plays an important role in the exclusion of xenobiotics from the brain (Probable). It confers to cells a resistance to multiple drugs and other xenobiotics including mitoxantrone, pheophorbide, camptothecin, methotrexate, azidothymidine, and the anthracyclines daunorubicin and doxorubicin, through the control of their efflux .
PMID:11306452 PMID:12477054 PMID:15670731 PMID:18056989 PMID:31254042
In placenta, it limits the penetration of drugs from the maternal plasma into the fetus (By similarity). May play a role in early stem cell self-renewal by blocking differentiation (By similarity).
In inflammatory macrophages, exports itaconate from the cytosol to the extracellular compartment and limits the activation of TFEB-dependent lysosome biogenesis involved in antibacterial innate immune response
PMID:11306452 PMID:12958161 PMID:19506252 PMID:20705604 PMID:28554189 PMID:30405239 PMID:31003562
Involved in porphyrin homeostasis, mediating the export of protoporphyrin IX (PPIX) from both mitochondria to cytosol and cytosol to extracellular space, it also functions in the cellular export of heme .
PMID:20705604 PMID:23189181
Also mediates the efflux of sphingosine-1-P from cells .
PMID:20110355
Acts as a urate exporter functioning in both renal and extrarenal urate excretion .
PMID:19506252 PMID:20368174 PMID:22132962 PMID:31003562 PMID:36749388
In kidney, it also functions as a physiological exporter of the uremic toxin indoxyl sulfate (By similarity). Also involved in the excretion of steroids like estrone 3-sulfate/E1S, 3beta-sulfooxy-androst-5-en-17-one/DHEAS, and other sulfate conjugates .
PMID:12682043 PMID:28554189 PMID:30405239
Mediates the secretion of the riboflavin and biotin vitamins into milk (By similarity). Extrudes pheophorbide a, a phototoxic porphyrin catabolite of chlorophyll, reducing its bioavailability (By similarity).
Plays an important role in the exclusion of xenobiotics from the brain (Probable). It confers to cells a resistance to multiple drugs and other xenobiotics including mitoxantrone, pheophorbide, camptothecin, methotrexate, azidothymidine, and the anthracyclines daunorubicin and doxorubicin, through the control of their efflux .
PMID:11306452 PMID:12477054 PMID:15670731 PMID:18056989 PMID:31254042
In placenta, it limits the penetration of drugs from the maternal plasma into the fetus (By similarity). May play a role in early stem cell self-renewal by blocking differentiation (By similarity).
In inflammatory macrophages, exports itaconate from the cytosol to the extracellular compartment and limits the activation of TFEB-dependent lysosome biogenesis involved in antibacterial innate immune response
Solute carrier organic anion transporter family member 1B1
SLCO1B1
substrate
Specific functionbile acid transmembrane transporter activity
Cellular location
Basolateral cell membrane
General function & pharmacology
Mediates the Na(+)-independent uptake of organic anions .
PMID:10358072 PMID:15159445 PMID:17412826
Shows broad substrate specificity, can transport both organic anions such as bile acid taurocholate (cholyltaurine) and conjugated steroids (dehydroepiandrosterone 3-sulfate, 17-beta-glucuronosyl estradiol, and estrone 3-sulfate), as well as eicosanoids (prostaglandin E2, thromboxane B2, leukotriene C4, and leukotriene E4), and thyroid hormones (T4/L-thyroxine, and T3/3,3',5'-triiodo-L-thyronine) .
PMID:10358072 PMID:10601278 PMID:10873595 PMID:11159893 PMID:12196548 PMID:12568656 PMID:15159445 PMID:15970799 PMID:16627748 PMID:17412826 PMID:19129463 PMID:26979622
Can take up bilirubin glucuronides from plasma into the liver, contributing to the detoxification-enhancing liver-blood shuttling loop .
PMID:22232210
Involved in the clearance of endogenous and exogenous substrates from the liver .
PMID:10358072 PMID:10601278
Transports coproporphyrin I and III, by-products of heme synthesis, and may be involved in their hepatic disposition .
PMID:26383540
May contribute to regulate the transport of organic compounds in testes across the blood-testis-barrier (Probable). Can transport HMG-CoA reductase inhibitors (also known as statins), such as pravastatin and pitavastatin, a clinically important class of hypolipidemic drugs .
PMID:10601278 PMID:15159445 PMID:15970799
May play an important role in plasma and tissue distribution of the structurally diverse chemotherapeutic drug methotrexate .
PMID:23243220
May also transport antihypertension agents, such as the angiotensin-converting enzyme (ACE) inhibitor prodrug enalapril, and the highly selective angiotensin II AT1-receptor antagonist valsartan, in the liver .
PMID:16624871 PMID:16627748
Shows a pH-sensitive substrate specificity towards prostaglandin E2 and T4 which may be ascribed to the protonation state of the binding site and leads to a stimulation of substrate transport in an acidic microenvironment .
PMID:19129463
Hydrogencarbonate/HCO3(-) acts as the probable counteranion that exchanges for organic anions PMID:19129463
PMID:10358072 PMID:15159445 PMID:17412826
Shows broad substrate specificity, can transport both organic anions such as bile acid taurocholate (cholyltaurine) and conjugated steroids (dehydroepiandrosterone 3-sulfate, 17-beta-glucuronosyl estradiol, and estrone 3-sulfate), as well as eicosanoids (prostaglandin E2, thromboxane B2, leukotriene C4, and leukotriene E4), and thyroid hormones (T4/L-thyroxine, and T3/3,3',5'-triiodo-L-thyronine) .
PMID:10358072 PMID:10601278 PMID:10873595 PMID:11159893 PMID:12196548 PMID:12568656 PMID:15159445 PMID:15970799 PMID:16627748 PMID:17412826 PMID:19129463 PMID:26979622
Can take up bilirubin glucuronides from plasma into the liver, contributing to the detoxification-enhancing liver-blood shuttling loop .
PMID:22232210
Involved in the clearance of endogenous and exogenous substrates from the liver .
PMID:10358072 PMID:10601278
Transports coproporphyrin I and III, by-products of heme synthesis, and may be involved in their hepatic disposition .
PMID:26383540
May contribute to regulate the transport of organic compounds in testes across the blood-testis-barrier (Probable). Can transport HMG-CoA reductase inhibitors (also known as statins), such as pravastatin and pitavastatin, a clinically important class of hypolipidemic drugs .
PMID:10601278 PMID:15159445 PMID:15970799
May play an important role in plasma and tissue distribution of the structurally diverse chemotherapeutic drug methotrexate .
PMID:23243220
May also transport antihypertension agents, such as the angiotensin-converting enzyme (ACE) inhibitor prodrug enalapril, and the highly selective angiotensin II AT1-receptor antagonist valsartan, in the liver .
PMID:16624871 PMID:16627748
Shows a pH-sensitive substrate specificity towards prostaglandin E2 and T4 which may be ascribed to the protonation state of the binding site and leads to a stimulation of substrate transport in an acidic microenvironment .
PMID:19129463
Hydrogencarbonate/HCO3(-) acts as the probable counteranion that exchanges for organic anions PMID:19129463
Solute carrier organic anion transporter family member 1B3
SLCO1B3
substrate
Specific functionbile acid transmembrane transporter activity
Cellular location
Basolateral cell membrane
General function & pharmacology
Mediates the Na(+)-independent uptake of organic anions .
PMID:10779507 PMID:15159445 PMID:17412826
Shows broad substrate specificity, can transport both organic anions such as bile acid taurocholate (cholyltaurine) and conjugated steroids (17-beta-glucuronosyl estradiol, dehydroepiandrosterone sulfate (DHEAS), and estrone 3-sulfate), as well as eicosanoid leukotriene C4, prostaglandin E2 and L-thyroxine (T4) .
PMID:10779507 PMID:11159893 PMID:12568656 PMID:15159445 PMID:17412826 PMID:19129463
Hydrogencarbonate/HCO3(-) acts as the probable counteranion that exchanges for organic anions .
PMID:19129463
Shows a pH-sensitive substrate specificity towards sulfated steroids, taurocholate and T4 which may be ascribed to the protonation state of the binding site and leads to a stimulation of substrate transport in an acidic microenvironment .
PMID:19129463
Involved in the clearance of bile acids and organic anions from the liver .
PMID:22232210
Can take up bilirubin glucuronides from plasma into the liver, contributing to the detoxification-enhancing liver-blood shuttling loop .
PMID:22232210
Transports coproporphyrin I and III, by-products of heme synthesis, and may be involved in their hepatic disposition .
PMID:26383540
May contribute to regulate the transport of organic compounds in testes across the blood-testis-barrier (Probable). Can transport HMG-CoA reductase inhibitors (also known as statins) such as pitavastatin, a clinically important class of hypolipidemic drugs .
PMID:15159445
May play an important role in plasma and tissue distribution of the structurally diverse chemotherapeutic drugs methotrexate and paclitaxel .
PMID:23243220
May also transport antihypertension agents, such as the angiotensin-converting enzyme (ACE) inhibitor prodrug enalapril, and the highly selective angiotensin II AT1-receptor antagonist valsartan, in the liver PMID:16624871 PMID:16627748
PMID:10779507 PMID:15159445 PMID:17412826
Shows broad substrate specificity, can transport both organic anions such as bile acid taurocholate (cholyltaurine) and conjugated steroids (17-beta-glucuronosyl estradiol, dehydroepiandrosterone sulfate (DHEAS), and estrone 3-sulfate), as well as eicosanoid leukotriene C4, prostaglandin E2 and L-thyroxine (T4) .
PMID:10779507 PMID:11159893 PMID:12568656 PMID:15159445 PMID:17412826 PMID:19129463
Hydrogencarbonate/HCO3(-) acts as the probable counteranion that exchanges for organic anions .
PMID:19129463
Shows a pH-sensitive substrate specificity towards sulfated steroids, taurocholate and T4 which may be ascribed to the protonation state of the binding site and leads to a stimulation of substrate transport in an acidic microenvironment .
PMID:19129463
Involved in the clearance of bile acids and organic anions from the liver .
PMID:22232210
Can take up bilirubin glucuronides from plasma into the liver, contributing to the detoxification-enhancing liver-blood shuttling loop .
PMID:22232210
Transports coproporphyrin I and III, by-products of heme synthesis, and may be involved in their hepatic disposition .
PMID:26383540
May contribute to regulate the transport of organic compounds in testes across the blood-testis-barrier (Probable). Can transport HMG-CoA reductase inhibitors (also known as statins) such as pitavastatin, a clinically important class of hypolipidemic drugs .
PMID:15159445
May play an important role in plasma and tissue distribution of the structurally diverse chemotherapeutic drugs methotrexate and paclitaxel .
PMID:23243220
May also transport antihypertension agents, such as the angiotensin-converting enzyme (ACE) inhibitor prodrug enalapril, and the highly selective angiotensin II AT1-receptor antagonist valsartan, in the liver PMID:16624871 PMID:16627748
Carriers(1)
Proteins that carry this drug through the body
Albumin
ALB
binder
Specific functionantioxidant activity
Cellular location
Secreted
General function & pharmacology
Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transporter in plasma, typically binds about 80% of all plasma zinc .
PMID:19021548
Major calcium and magnesium transporter in plasma, binds approximately 45% of circulating calcium and magnesium in plasma (By similarity).
Potentially has more than two calcium-binding sites and might additionally bind calcium in a non-specific manner (By similarity). The shared binding site between zinc and calcium at residue Asp-273 suggests a crosstalk between zinc and calcium transport in the blood (By similarity). The rank order of affinity is zinc > calcium > magnesium (By similarity).
Binds to the bacterial siderophore enterobactin and inhibits enterobactin-mediated iron uptake of E.coli from ferric transferrin, and may thereby limit the utilization of iron and growth of enteric bacteria such as E.coli .
PMID:6234017
Does not prevent iron uptake by the bacterial siderophore aerobactin PMID:6234017
PMID:19021548
Major calcium and magnesium transporter in plasma, binds approximately 45% of circulating calcium and magnesium in plasma (By similarity).
Potentially has more than two calcium-binding sites and might additionally bind calcium in a non-specific manner (By similarity). The shared binding site between zinc and calcium at residue Asp-273 suggests a crosstalk between zinc and calcium transport in the blood (By similarity). The rank order of affinity is zinc > calcium > magnesium (By similarity).
Binds to the bacterial siderophore enterobactin and inhibits enterobactin-mediated iron uptake of E.coli from ferric transferrin, and may thereby limit the utilization of iron and growth of enteric bacteria such as E.coli .
PMID:6234017
Does not prevent iron uptake by the bacterial siderophore aerobactin PMID:6234017
Scientific references(7)
Aloy B., Tazi I., Bagnis C.I., Gauthier M., Janus N., Launay-Vacher V., Deray G., Tourret J.
Simultaneous Analysis of Elvitegravir, Tenofovir, Tenofovir Alafenamide, and Tenofovir Disoproxil Fumarate in Rabbit Plasma Using UPLC/MS/MS. doi: 10.
26226/morressier
57d6b2bed462b8028d88e659
Grant P.M., Cotter A.G.
Tenofovir and bone health.
Curr Opinion HIV AIDS
2016 May11(3):326-32. doi: 10.1097/COH.0000000000000248
Deeks E.D.
Bictegravir/Emtricitabine/Tenofovir Alafenamide: A Review in HIV-1 Infection.
Drugs
2018 Nov78(17):1817-1828. doi: 10.1007/s40265-018-1010-7
Ogawa E., Furusyo N., Nguyen M.H.
Tenofovir alafenamide in the treatment of chronic hepatitis B: design, development, and place in therapy.
Drug Des Devel Therapeutics
2017 Nov 611:3197-3204. doi: 10.2147/DDDT.S126742. eCollection 2017
Ray A.S., Fordyce M.W., Hitchcock M.J.
Tenofovir alafenamide: A novel prodrug of tenofovir for the treatment of Human Immunodeficiency Virus.
Antiviral Research
2016 Jan125:63-70. doi: 10.1016/j.antiviral.2015.11.009. Epub 2015 Nov 27
Antela A., Aguiar C., Compston J., Hendry B.M., Boffito M., Mallon P., Pourcher-Martinez V., Di Perri G.
The role of tenofovir alafenamide in future HIV management.
HIV Medicine
2016 May17 Suppl 2:4-16. doi: 10.1111/hiv.12401
Markowitz M., Zolopa A., Squires K., Ruane P., Coakley D., Kearney B., Zhong L., Wulfsohn M., Miller M.D., Lee W.A.
Phase I/II study of the pharmacokinetics, safety and antiretroviral activity of tenofovir alafenamide, a new prodrug of the HIV reverse transcriptase inhibitor tenofovir, in HIV-infected adults.
Journal Antimicrob Chemother
2014 May69(5):1362-9. doi: 10.1093/jac/dkt532. Epub 2014 Feb 6
ATC classification(7 codes)
ATC J05AR29
ATC J05AR19
ATC J05AR20
ATC J05AR17
ATC J05AF13
ATC J05AR22
ATC J05AR18
Affected organisms(3)
HIV-1
Herpes simplex virus
Hepatitis B virus
Salt forms(1)
Tenofovir alafenamide fumarate(DBSALT002533)
Experimental properties(5)
Chemical identifiers
CAS, UNII, InChI Key and database cross-references
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Chemical identifiers
CAS, UNII, InChI Key and database cross-references
Linked compound data from DrugBank Open Data (CC BY-NC 4.0)
Tenofovir alafenamide
Additional database identifiers
Drugs Product Database (DPD)
22668
ChemSpider
7849225
ZINC
ZINC000100055899
GenBank Gene Database
U28646
GenBank Protein Database
896047
UniProt Accession
Q72547_HV1
GenBank Gene Database
M15654
GenBank Protein Database
326388
UniProt Accession
POL_HV1B1
UniProt Accession
Q3MS49_HBV
UniProt Accession
I6TLU5_HHV21
HUGO Gene Nomenclature Committee (HGNC)
HGNC:9251
GeneCards
CTSA
Guide to Pharmacology
1581
UniProt Accession
PPGB_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:1863
GenAtlas
CES1
GeneCards
CES1
GenBank Gene Database
M73499
Guide to Pharmacology
2592
UniProt Accession
EST1_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:2637
GenAtlas
CYP3A4
GeneCards
CYP3A4
GenBank Gene Database
M18907
Guide to Pharmacology
1337
UniProt Accession
CP3A4_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:361
GenAtlas
AK1
GeneCards
AK1
GenBank Gene Database
J04809
GenBank Protein Database
178322
UniProt Accession
KAD1_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:362
GeneCards
AK2
UniProt Accession
KAD2_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:7849
GenAtlas
NME1
GeneCards
NME1
GenBank Gene Database
X75598
UniProt Accession
NDKA_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:7850
GenAtlas
NME2
GeneCards
NME2
GenBank Gene Database
X58965
UniProt Accession
NDKB_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:399
GenAtlas
ALB
GeneCards
ALB
GenBank Gene Database
V00494
GenBank Protein Database
28590
UniProt Accession
ALBU_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:40
GenAtlas
ABCB1
GeneCards
ABCB1
GenBank Gene Database
M14758
GenBank Protein Database
307180
Guide to Pharmacology
768
UniProt Accession
MDR1_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:55
GenAtlas
ABCC4
GeneCards
ABCC4
GenBank Gene Database
AF071202
GenBank Protein Database
3335173
Guide to Pharmacology
782
UniProt Accession
MRP4_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:10970
GenAtlas
hROAT1
GeneCards
SLC22A6
GenBank Gene Database
AF057039
GenBank Protein Database
3831566
Guide to Pharmacology
1025
UniProt Accession
S22A6_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:10972
GeneCards
SLC22A8
GenBank Gene Database
AF097491
GenBank Protein Database
4378059
Guide to Pharmacology
1027
UniProt Accession
S22A8_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:74
GenAtlas
ABCG2
GeneCards
ABCG2
GenBank Gene Database
AF103796
GenBank Protein Database
4185796
Guide to Pharmacology
792
UniProt Accession
ABCG2_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:10959
GenAtlas
SLCO1B1
GeneCards
SLCO1B1
GenBank Gene Database
AF060500
GenBank Protein Database
5051630
Guide to Pharmacology
1220
UniProt Accession
SO1B1_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:10961
GeneCards
SLCO1B3
GenBank Gene Database
AJ251506
GenBank Protein Database
9187497
Guide to Pharmacology
1221
UniProt Accession
SO1B3_HUMAN
DrugBank citations
If you use DrugBank data in your research, please cite:
- DrugBank 6.02024Recommended citationKnox C., Wilson M., Klinger C.M., et alDrugBank 6.0: the DrugBank Knowledgebase for 2024Nucleic Acids Res. 2024 Jan 552(D1):D1265-D1275
- DrugBank 5.02018Wishart D.S., Feunang Y.D., Guo A.C., et alDrugBank 5.0: a major update to the DrugBank database for 2018Nucleic Acids Res. 2017 Nov 846(D1):D1074-D1082
- DrugBank 4.02014Law V., Knox C., Djoumbou Y., et alDrugBank 4.0: shedding new light on drug metabolismNucleic Acids Res. 2014 Jan 142(1):D1091-7
- DrugBank 3.02011Knox C., Law V., Jewison T., et alDrugBank 3.0: a comprehensive resource for 'omics' research on drugsNucleic Acids Res. 2011 Jan39(Database issue):D1035-41
- DrugBank 2.02008Wishart D.S., Knox C., Guo A.C., et alDrugBank: a knowledgebase for drugs, drug actions and drug targets.Nucleic Acids Research2008 Jan36(Database issue):D901-6
- DrugBank 1.02006Wishart D.S., Knox C., Guo A.C., et alDrugBank: a comprehensive resource for in silico drug discovery and exploration.Nucleic Acids Research2006 Jan 134(Database issue):D668-72
Source: go.drugbank.comCC BY-NC 4.0
Updated 8 Mar 2026