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Identification
- Summary
Etravirine is a non-nucleoside reverse transcriptase inhibitor (NNRTI) used in the treatment of HIV-1 infections in combination with other antiretroviral agents.
- Brand Names
- Intelence
- Generic Name
- Etravirine
- DrugBank Accession Number
- DB06414
- Background
Etravirine is an antiretroviral agent more specifically classified as a Non-Nucleoside Reverse Transcriptase Inhibitor (NNRTI). Etraverine is used clinically for the treatment of human immunodeficiency virus type 1 (HIV-1) infection. On January 18, 2007, the FDA granted accelerated approved for the use of etravirine 100mg tablets in the treatment of adult HIV-1 infection documented to be resistant to therapy with other NNRTIs and antiretroviral agents. On March 26, 2012, approval was extended for use in treatment-experienced pediatric patients 6 to 18 years of age, weighing at least 16 kg. Etravarine must always be used in combination with other antiretroviral drugs.
Etravirine exerts its effects via direct inhibition of the reverse transcriptase enzyme of human immunodeficiency virus type 1 (HIV-1), and consequently blocks DNA-dependent and RNA-dependent polymerase activity. Etravirine does not inhibit human DNA polymerase alpha, beta or gamma.
Common side effects of use include mild to moderate rash within the first 6 weeks of therapy, nausea, diarrhea and peripheral neuropathy. Patients are advised to immediately contact their healthcare provider if a rash develops.
In 2009, postmarketing case reports of Stevens-Johnson Syndrome, toxic epidermal necrolysis, erythema multiforme, and other hypersensitivity reactions lead to a revision of etravirine's "Warnings and Precautions," as well as notification of health care providers.
In 2013, reports of Autoimmune disorders (such as Graves’ disease, polymyositis, and Guillain-Barré syndrome) in the setting of immune reconstitution, as well as more in depth information about the development of rashes in patients taking etravirine, lead to a modification of etravirine's monograph.
- Type
- Small Molecule
- Groups
- Approved
- Structure
Structure for Etravirine (DB06414)
- Weight
- Average: 435.277
Monoisotopic: 434.049071779 - Chemical Formula
- C20H15BrN6O
- Synonyms
- Etravirina
- Etravirine
- External IDs
- R-165335
- R165335
- TMC 125
- TMC-125
- TMC125
Pharmacology
- Indication
Etravirine is indicated, in combination with other antiretroviral agents, for the treatment of HIV-1 infection in treatment-experienced patients ≥2 years of age.1
Reduce drug development failure ratesBuild, train, & validate machine-learning modelswith evidence-based and structured datasets.Build, train, & validate predictive machine-learning models with structured datasets.- Associated Conditions
Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Adjunct therapy in treatment of Human immunodeficiency virus type 1 (hiv-1) infection •••••••••••• ••••••••• ••••••••••• •••••• - Contraindications & Blackbox Warnings
Prevent Adverse Drug Events TodayTap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events with our Clinical API- Pharmacodynamics
Clinical trials have shown no prolongation of QT intervals on electrocardiograms after 8 days of dosing.
- Mechanism of action
Etravirine exerts its effects via direct inhibition of the reverse transcriptase enzyme of human immunodeficiency virus type 1 (HIV-1). It directly binds reverse transcriptase and consequently blocks DNA-dependent and RNA-dependent polymerase activity. Etravirine does not inhibit human DNA polymerase alpha, beta or gamma.
Target Actions Organism AGag-Pol polyprotein modulatorUGag-Pol polyprotein Not Available UReverse transcriptase/RNaseH inhibitorHuman immunodeficiency virus 1 - Absorption
Maximum oral absorption is achieved in 2.5-4 hours.
Absorption is unaffected by the concomitant use of oral ranitidine or omeprazole, which decrease gastric acidity.
Administration under fasting conditions resulted in a near 50% decrease in systemic exposure (AUC) when compared to administration after a meal.
- Volume of distribution
Distribution of etravirine into compartments other than plasma has not been evaluated in humans.
- Protein binding
Plasma protein binding is about 99.9% in vitro. In vitro, 99.6% is bound to albumin, and 97.66% - 99.02% is bound to 1-alpha glycoprotein.
- Metabolism
Metabolized (in vitro) by the liver CYP450 enzymes: CYP3A4, CYP2C9, CYP2C19. The major metabolites formed by a methyl hydroxylation of the dimethylbenzonitrile moiety retained less than 90% of etravirine's activity.
- Route of elimination
After a 800mg dose of radio-labelled etraverine, 93.7% was found to undergo fecal elimination, with 81.2% - 86.4% eliminated unchanged. 1.2% of the dose was renally eliminated, changed.
Etravirine is dialyzable (hemodialysis).
- Half-life
Half life of 9.05-41 hours.
- Clearance
Renal clearance of etravirine is negligible (<1.2%), thus no dose adjustments are required in patients with renal impairment.
Clearance is shown to be reduced in patients with Hepatitis B and/or co-infection, however, the safety profile of etravirine does not call for dosage adjustments.
- Adverse Effects
Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!Improve decision support & research outcomes with our structured adverse effects data.- Toxicity
Not Available
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your softwareAbametapir The serum concentration of Etravirine can be increased when it is combined with Abametapir. Abatacept The metabolism of Etravirine can be increased when combined with Abatacept. Abemaciclib The metabolism of Abemaciclib can be increased when combined with Etravirine. Abrocitinib The metabolism of Abrocitinib can be decreased when combined with Etravirine. Acalabrutinib The metabolism of Acalabrutinib can be increased when combined with Etravirine. - Food Interactions
- Avoid grapefruit products. Grapefruit inhibits the CYP3A metabolism of etravirine, which may increase its serum concentration.
- Avoid St. John's Wort. This herb induces the CYP3A metabolism of etravirine and may reduce its serum concentration.
- Take after a meal. Take after meals. This increases the bioavailability of etravirine.
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Intelence Tablet 200 mg/1 Oral A-S Medication Solutions 2010-12-22 Not applicable US 
Intelence Tablet 100 mg/1 Oral State of Florida DOH Central Pharmacy 2009-07-01 Not applicable US Intelence Tablet 200 mg Oral Janssen Pharmaceuticals 2011-12-12 Not applicable Canada 
Intelence Tablet 200 mg/1 Oral Janssen Products, LP 2010-12-22 Not applicable US Intelence Tablet 200 mg/1 Oral Physicians Total Care, Inc. 2012-10-10 Not applicable US - Generic Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Etravirine Tablet 100 mg/1 Oral Amneal Pharmaceuticals NY LLC 2021-06-14 Not applicable US Etravirine Tablet 25 mg/1 Oral Amneal Pharmaceuticals NY LLC 2021-06-14 Not applicable US Etravirine Tablet 100 mg/1 Oral AvKARE 2022-10-04 Not applicable US Etravirine Tablet 200 mg/1 Oral Leading Pharma, Llc 2022-06-05 Not applicable US Etravirine Tablet 200 mg/1 Oral Amneal Pharmaceuticals NY LLC 2021-06-14 Not applicable US
Categories
- ATC Codes
- J05AG04 — Etravirine
- Drug Categories
- Anti-Infective Agents
- Anti-Retroviral Agents
- Antiinfectives for Systemic Use
- Antiviral Agents
- Antivirals for Systemic Use
- Cytochrome P-450 CYP2C19 Inhibitors
- Cytochrome P-450 CYP2C19 inhibitors (strength unknown)
- Cytochrome P-450 CYP2C19 Substrates
- Cytochrome P-450 CYP2C9 Inhibitors
- Cytochrome P-450 CYP2C9 Inhibitors (strength unknown)
- Cytochrome P-450 CYP2C9 Substrates
- Cytochrome P-450 CYP3A Inducers
- Cytochrome P-450 CYP3A Substrates
- Cytochrome P-450 CYP3A4 Inducers
- Cytochrome P-450 CYP3A4 Inducers (moderate)
- Cytochrome P-450 CYP3A4 Substrates
- Cytochrome P-450 Enzyme Inducers
- Cytochrome P-450 Enzyme Inhibitors
- Cytochrome P-450 Substrates
- Direct Acting Antivirals
- Enzyme Inhibitors
- Human Immunodeficiency Virus 1 Non-Nucleoside Analog Reverse Transcriptase Inhibitor
- Non-Nucleoside Reverse Transcriptase Inhibitors
- Nonnucleoside Reverse Transcriptase Inhibitors
- Nucleic Acid Synthesis Inhibitors
- P-glycoprotein inhibitors
- Reverse Transcriptase Inhibitors
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as diarylethers. These are organic compounds containing the dialkyl ether functional group, with the formula ROR', where R and R' are aryl groups.
- Kingdom
- Organic compounds
- Super Class
- Organic oxygen compounds
- Class
- Organooxygen compounds
- Sub Class
- Ethers
- Direct Parent
- Diarylethers
- Alternative Parents
- Aniline and substituted anilines / Benzonitriles / Phenol ethers / Phenoxy compounds / m-Xylenes / Halopyrimidines / Aminopyrimidines and derivatives / Imidolactams / Aryl bromides / Heteroaromatic compounds show 7 more
- Substituents
- Amine / Aminopyrimidine / Aniline or substituted anilines / Aromatic heteromonocyclic compound / Aryl bromide / Aryl halide / Azacycle / Benzenoid / Benzonitrile / Carbonitrile show 20 more
- Molecular Framework
- Aromatic heteromonocyclic compounds
- External Descriptors
- organobromine compound, aromatic ether, aminopyrimidine, dinitrile (CHEBI:63589)
- Affected organisms
- Not Available
Chemical Identifiers
- UNII
- 0C50HW4FO1
- CAS number
- 269055-15-4
- InChI Key
- PYGWGZALEOIKDF-UHFFFAOYSA-N
- InChI
- InChI=1S/C20H15BrN6O/c1-11-7-14(10-23)8-12(2)17(11)28-19-16(21)18(24)26-20(27-19)25-15-5-3-13(9-22)4-6-15/h3-8H,1-2H3,(H3,24,25,26,27)
- IUPAC Name
- 4-({6-amino-5-bromo-2-[(4-cyanophenyl)amino]pyrimidin-4-yl}oxy)-3,5-dimethylbenzonitrile
- SMILES
- CC1=CC(=CC(C)=C1OC1=C(Br)C(N)=NC(NC2=CC=C(C=C2)C#N)=N1)C#N
References
- General References
- FDA Approved Drug Products: Intelence (etravirine) tablets for oral use [Link]
- External Links
- KEGG Drug
- D04112
- PubChem Compound
- 193962
- PubChem Substance
- 175427070
- ChemSpider
- 168313
- BindingDB
- 50103642
- 475969
- ChEBI
- 63589
- ChEMBL
- CHEMBL308954
- ZINC
- ZINC000000602632
- PharmGKB
- PA166014703
- PDBe Ligand
- 65B
- RxList
- RxList Drug Page
- Drugs.com
- Drugs.com Drug Page
- Wikipedia
- Etravirine
- PDB Entries
- 1sv5 / 3m8p
- FDA label
- Download (642 KB)
- MSDS
- Download (122 KB)
Clinical Trials
- Clinical Trials
Clinical Trial & Rare Diseases Add-on Data Package
Explore 4,000+ rare diseases, orphan drugs & condition pairs, clinical trial why stopped data, & more. Preview package Phase Status Purpose Conditions Count Start Date Why Stopped 100+ additional columns Unlock 175K+ rows when you subscribe.View sample dataNot Available Completed Not Available Acquired Immune Deficiency Syndrome (AIDS) 1 somestatus stop reason just information to hide Not Available Completed Not Available Coronavirus Disease 2019 (COVID‑19) / Human Immunodeficiency Virus (HIV) Infections 1 somestatus stop reason just information to hide Not Available Completed Not Available Hepatitis C Virus (HCV) Infection / Human Immunodeficiency Virus (HIV) Infections 1 somestatus stop reason just information to hide Not Available Completed Not Available Human Immunodeficiency Virus (HIV) Infections 5 somestatus stop reason just information to hide Not Available Completed Treatment Sleep disorders and disturbances 1 somestatus stop reason just information to hide
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Tablet Oral Tablet Oral 100 mg/1 Tablet Oral 100 mg Tablet Oral 200 mg/1 Tablet Oral 25 mg/1 Tablet Oral 25 mg Tablet Oral 25.00 mg Tablet Oral 200 mg/tablet Tablet Oral 200 mg - Prices
- Not Available
- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region CA2651665 No 2010-04-27 2027-06-06 Canada CA2350801 No 2008-05-20 2019-09-24 Canada US6878717 Yes 2005-04-12 2020-05-05 US US7037917 Yes 2006-05-02 2021-06-13 US US8003789 Yes 2011-08-23 2020-05-01 US US7887845 Yes 2011-02-15 2019-09-25 US
Properties
- State
- Solid
- Experimental Properties
- Not Available
- Predicted Properties
Property Value Source Water Solubility 0.0169 mg/mL ALOGPS logP 3.67 ALOGPS logP 5.54 Chemaxon logS -4.4 ALOGPS pKa (Strongest Acidic) 10.99 Chemaxon pKa (Strongest Basic) 3.49 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 6 Chemaxon Hydrogen Donor Count 2 Chemaxon Polar Surface Area 120.64 Å2 Chemaxon Rotatable Bond Count 4 Chemaxon Refractivity 111.87 m3·mol-1 Chemaxon Polarizability 41.09 Å3 Chemaxon Number of Rings 3 Chemaxon Bioavailability 1 Chemaxon Rule of Five No Chemaxon Ghose Filter Yes Chemaxon Veber's Rule No Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
- Not Available
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 182.81187 predictedDeepCCS 1.0 (2019) [M+H]+ 185.16988 predictedDeepCCS 1.0 (2019) [M+Na]+ 191.87468 predictedDeepCCS 1.0 (2019)
Targets
Build, predict & validate machine-learning models
Use our structured and evidence-based datasets to unlock newinsights and accelerate drug research.
Use our structured and evidence-based datasets to unlock new insights and accelerate drug research.
- Kind
- Protein
- Organism
- Not Available
- Pharmacological action
- Yes
- Actions
- Modulator
- General Function
- Gag-Pol polyprotein Mediates, with Gag polyprotein, the essential events in virion assembly, including binding the plasma membrane, making the protein-protein interactions necessary to create spherical particles, recruiting the viral Env proteins, and packaging the genomic RNA via direct interactions with the RNA packaging sequence (Psi). Gag-Pol polyprotein may regulate its own translation, by the binding genomic RNA in the 5'-UTR. At low concentration, the polyprotein would promote translation, whereas at high concentration, the polyprotein would encapsidate genomic RNA and then shut off translation.
- Specific Function
- aspartic-type endopeptidase activity
- Gene Name
- gag-pol
- Uniprot ID
- P03366
- Uniprot Name
- Gag-Pol polyprotein
- Molecular Weight
- 163287.51 Da
References
- Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. [Article]
- Zhou Y, Zhang Y, Zhao D, Yu X, Shen X, Zhou Y, Wang S, Qiu Y, Chen Y, Zhu F: TTD: Therapeutic Target Database describing target druggability information. Nucleic Acids Res. 2024 Jan 5;52(D1):D1465-D1477. doi: 10.1093/nar/gkad751. [Article]
- Kind
- Protein
- Organism
- Not Available
- Pharmacological action
- Unknown
- General Function
- Gag-Pol polyprotein Mediates, with Gag polyprotein, the essential events in virion assembly, including binding the plasma membrane, making the protein-protein interactions necessary to create spherical particles, recruiting the viral Env proteins, and packaging the genomic RNA via direct interactions with the RNA packaging sequence (Psi). Gag-Pol polyprotein may regulate its own translation, by the binding genomic RNA in the 5'-UTR. At low concentration, the polyprotein would promote translation, whereas at high concentration, the polyprotein would encapsidate genomic RNA and then shut off translation.
- Specific Function
- aspartic-type endopeptidase activity
- Gene Name
- gag-pol
- Uniprot ID
- P04585
- Uniprot Name
- Gag-Pol polyprotein
- Molecular Weight
- 162041.05 Da
References
- Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. [Article]
- Kind
- Protein
- Organism
- Human immunodeficiency virus 1
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Not Available
- Specific Function
- aspartic-type endopeptidase activity
- Gene Name
- pol
- Uniprot ID
- Q72547
- Uniprot Name
- Reverse transcriptase/RNaseH
- Molecular Weight
- 65223.615 Da
References
- De Clercq E: Emerging anti-HIV drugs. Expert Opin Emerg Drugs. 2005 May;10(2):241-73. [Article]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- SubstrateInducer
- General Function
- A cytochrome P450 monooxygenase involved in the metabolism of sterols, steroid hormones, retinoids and fatty acids (PubMed:10681376, PubMed:11093772, PubMed:11555828, PubMed:12865317, PubMed:14559847, PubMed:15373842, PubMed:15764715, PubMed:19965576, PubMed:20702771, PubMed:21490593, PubMed:21576599). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase). Catalyzes the hydroxylation of carbon-hydrogen bonds (PubMed:12865317, PubMed:14559847, PubMed:15373842, PubMed:15764715, PubMed:21490593, PubMed:21576599, PubMed:2732228). Exhibits high catalytic activity for the formation of hydroxyestrogens from estrone (E1) and 17beta-estradiol (E2), namely 2-hydroxy E1 and E2, as well as D-ring hydroxylated E1 and E2 at the C-16 position (PubMed:11555828, PubMed:12865317, PubMed:14559847). Plays a role in the metabolism of androgens, particularly in oxidative deactivation of testosterone (PubMed:15373842, PubMed:15764715, PubMed:22773874, PubMed:2732228). Metabolizes testosterone to less biologically active 2beta- and 6beta-hydroxytestosterones (PubMed:15373842, PubMed:15764715, PubMed:2732228). Contributes to the formation of hydroxycholesterols (oxysterols), particularly A-ring hydroxylated cholesterol at the C-4beta position, and side chain hydroxylated cholesterol at the C-25 position, likely contributing to cholesterol degradation and bile acid biosynthesis (PubMed:21576599). Catalyzes bisallylic hydroxylation of polyunsaturated fatty acids (PUFA) (PubMed:9435160). Catalyzes the epoxidation of double bonds of PUFA with a preference for the last double bond (PubMed:19965576). Metabolizes endocannabinoid arachidonoylethanolamide (anandamide) to 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acid ethanolamides (EpETrE-EAs), potentially modulating endocannabinoid system signaling (PubMed:20702771). Plays a role in the metabolism of retinoids. Displays high catalytic activity for oxidation of all-trans-retinol to all-trans-retinal, a rate-limiting step for the biosynthesis of all-trans-retinoic acid (atRA) (PubMed:10681376). Further metabolizes atRA toward 4-hydroxyretinoate and may play a role in hepatic atRA clearance (PubMed:11093772). Responsible for oxidative metabolism of xenobiotics. Acts as a 2-exo-monooxygenase for plant lipid 1,8-cineole (eucalyptol) (PubMed:11159812). Metabolizes the majority of the administered drugs. Catalyzes sulfoxidation of the anthelmintics albendazole and fenbendazole (PubMed:10759686). Hydroxylates antimalarial drug quinine (PubMed:8968357). Acts as a 1,4-cineole 2-exo-monooxygenase (PubMed:11695850). Also involved in vitamin D catabolism and calcium homeostasis. Catalyzes the inactivation of the active hormone calcitriol (1-alpha,25-dihydroxyvitamin D(3)) (PubMed:29461981)
- Specific Function
- 1,8-cineole 2-exo-monooxygenase activity
- Gene Name
- CYP3A4
- Uniprot ID
- P08684
- Uniprot Name
- Cytochrome P450 3A4
- Molecular Weight
- 57342.67 Da
References
- Perez VE, Sanchez-Parra C, Serrano Villar S: [Etravirine drug interactions]. Enferm Infecc Microbiol Clin. 2009 Dec;27 Suppl 2:27-31. doi: 10.1016/S0213-005X(09)73216-1. [Article]
- Kakuda TN, Scholler-Gyure M, Hoetelmans RM: Pharmacokinetic interactions between etravirine and non-antiretroviral drugs. Clin Pharmacokinet. 2011 Jan;50(1):25-39. doi: 10.2165/11534740-000000000-00000. [Article]
- Scholler-Gyure M, Kakuda TN, Raoof A, De Smedt G, Hoetelmans RM: Clinical pharmacokinetics and pharmacodynamics of etravirine. Clin Pharmacokinet. 2009;48(9):561-74. doi: 10.2165/10895940-000000000-00000. [Article]
- FDA Drug Development and Drug Interactions: Table of Substrates, Inhibitors and Inducers [Link]
- Intelence (Etravirine) FDA Label [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- SubstrateInhibitor
- General Function
- A cytochrome P450 monooxygenase involved in the metabolism of various endogenous substrates, including fatty acids and steroids (PubMed:12865317, PubMed:15766564, PubMed:19965576, PubMed:21576599, PubMed:7574697, PubMed:9435160, PubMed:9866708). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (PubMed:12865317, PubMed:15766564, PubMed:19965576, PubMed:21576599, PubMed:7574697, PubMed:9435160, PubMed:9866708). Catalyzes the epoxidation of double bonds of polyunsaturated fatty acids (PUFA) (PubMed:15766564, PubMed:19965576, PubMed:7574697, PubMed:9866708). Catalyzes the hydroxylation of carbon-hydrogen bonds. Metabolizes cholesterol toward 25-hydroxycholesterol, a physiological regulator of cellular cholesterol homeostasis (PubMed:21576599). Exhibits low catalytic activity for the formation of catechol estrogens from 17beta-estradiol (E2) and estrone (E1), namely 2-hydroxy E1 and E2 (PubMed:12865317). Catalyzes bisallylic hydroxylation and hydroxylation with double-bond migration of polyunsaturated fatty acids (PUFA) (PubMed:9435160, PubMed:9866708). Also metabolizes plant monoterpenes such as limonene. Oxygenates (R)- and (S)-limonene to produce carveol and perillyl alcohol (PubMed:11950794). Contributes to the wide pharmacokinetics variability of the metabolism of drugs such as S-warfarin, diclofenac, phenytoin, tolbutamide and losartan (PubMed:25994031)
- Specific Function
- (R)-limonene 6-monooxygenase activity
- Gene Name
- CYP2C9
- Uniprot ID
- P11712
- Uniprot Name
- Cytochrome P450 2C9
- Molecular Weight
- 55627.365 Da
References
- Perez VE, Sanchez-Parra C, Serrano Villar S: [Etravirine drug interactions]. Enferm Infecc Microbiol Clin. 2009 Dec;27 Suppl 2:27-31. doi: 10.1016/S0213-005X(09)73216-1. [Article]
- Kakuda TN, Scholler-Gyure M, Hoetelmans RM: Pharmacokinetic interactions between etravirine and non-antiretroviral drugs. Clin Pharmacokinet. 2011 Jan;50(1):25-39. doi: 10.2165/11534740-000000000-00000. [Article]
- Scholler-Gyure M, Kakuda TN, Raoof A, De Smedt G, Hoetelmans RM: Clinical pharmacokinetics and pharmacodynamics of etravirine. Clin Pharmacokinet. 2009;48(9):561-74. doi: 10.2165/10895940-000000000-00000. [Article]
- Scholler-Gyure M, Kakuda TN, De Smedt G, Vanaken H, Bouche MP, Peeters M, Woodfall B, Hoetelmans RM: A pharmacokinetic study of etravirine (TMC125) co-administered with ranitidine and omeprazole in HIV-negative volunteers. Br J Clin Pharmacol. 2008 Oct;66(4):508-16. doi: 10.1111/j.1365-2125.2008.03214.x. Epub 2008 Apr 25. [Article]
- Etravirine FDA label [File]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- SubstrateInhibitor
- Curator comments
- There is conflicting information in the literature regarding the severity of inhibition of CYP2C19, with some sources suggesting weak inhibition [A15663], some suggesting moderate inhibition [F1510], and some general comments regarding CYP2C19 inhibition [A15662, A15664, A38838].
- General Function
- A cytochrome P450 monooxygenase involved in the metabolism of polyunsaturated fatty acids (PUFA) (PubMed:18577768, PubMed:19965576, PubMed:20972997). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (PubMed:18577768, PubMed:19965576, PubMed:20972997). Catalyzes the hydroxylation of carbon-hydrogen bonds. Hydroxylates PUFA specifically at the omega-1 position (PubMed:18577768). Catalyzes the epoxidation of double bonds of PUFA (PubMed:19965576, PubMed:20972997). Also metabolizes plant monoterpenes such as limonene. Oxygenates (R)- and (S)-limonene to produce carveol and perillyl alcohol (PubMed:11950794). Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and imipramine. Hydroxylates fenbendazole at the 4' position (PubMed:23959307)
- Specific Function
- (R)-limonene 6-monooxygenase activity
- Gene Name
- CYP2C19
- Uniprot ID
- P33261
- Uniprot Name
- Cytochrome P450 2C19
- Molecular Weight
- 55944.565 Da
References
- Perez VE, Sanchez-Parra C, Serrano Villar S: [Etravirine drug interactions]. Enferm Infecc Microbiol Clin. 2009 Dec;27 Suppl 2:27-31. doi: 10.1016/S0213-005X(09)73216-1. [Article]
- Kakuda TN, Scholler-Gyure M, Hoetelmans RM: Pharmacokinetic interactions between etravirine and non-antiretroviral drugs. Clin Pharmacokinet. 2011 Jan;50(1):25-39. doi: 10.2165/11534740-000000000-00000. [Article]
- Scholler-Gyure M, Kakuda TN, Raoof A, De Smedt G, Hoetelmans RM: Clinical pharmacokinetics and pharmacodynamics of etravirine. Clin Pharmacokinet. 2009;48(9):561-74. doi: 10.2165/10895940-000000000-00000. [Article]
- Yanakakis LJ, Bumpus NN: Biotransformation of the antiretroviral drug etravirine: metabolite identification, reaction phenotyping, and characterization of autoinduction of cytochrome P450-dependent metabolism. Drug Metab Dispos. 2012 Apr;40(4):803-14. doi: 10.1124/dmd.111.044404. Epub 2012 Jan 23. [Article]
- Viani RM: Role of etravirine in the management of treatment-experienced patients with human immunodeficiency virus type 1. HIV AIDS (Auckl). 2010;2:141-9. Epub 2010 Jun 28. [Article]
- Selected Properties of Etravirine, HIVCLINIC.ca [File]
Transporters
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Translocates drugs and phospholipids across the membrane (PubMed:2897240, PubMed:35970996, PubMed:8898203, PubMed:9038218). 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 (PubMed:8898203). Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells (PubMed:2897240, PubMed:35970996, PubMed:9038218)
- Specific Function
- ABC-type xenobiotic transporter activity
- Gene Name
- ABCB1
- Uniprot ID
- P08183
- Uniprot Name
- ATP-dependent translocase ABCB1
- Molecular Weight
- 141477.255 Da
References
- Kakuda TN, Scholler-Gyure M, Hoetelmans RM: Pharmacokinetic interactions between etravirine and non-antiretroviral drugs. Clin Pharmacokinet. 2011 Jan;50(1):25-39. doi: 10.2165/11534740-000000000-00000. [Article]
- Scholler-Gyure M, Kakuda TN, Raoof A, De Smedt G, Hoetelmans RM: Clinical pharmacokinetics and pharmacodynamics of etravirine. Clin Pharmacokinet. 2009;48(9):561-74. doi: 10.2165/10895940-000000000-00000. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Energy-dependent phospholipid efflux translocator that acts as a positive regulator of biliary lipid secretion. Functions as a floppase that translocates specifically phosphatidylcholine (PC) from the inner to the outer leaflet of the canalicular membrane bilayer into the canaliculi of hepatocytes. Translocation of PC makes the biliary phospholipids available for extraction into the canaliculi lumen by bile salt mixed micelles and therefore protects the biliary tree from the detergent activity of bile salts (PubMed:17523162, PubMed:21820390, PubMed:23468132, PubMed:24594635, PubMed:24723470, PubMed:24806754, PubMed:31873305, PubMed:7957936, PubMed:8898203, PubMed:9366571). Plays a role in the recruitment of phosphatidylcholine (PC), phosphatidylethanolamine (PE) and sphingomyelin (SM) molecules to nonraft membranes and to further enrichment of SM and cholesterol in raft membranes in hepatocytes (PubMed:23468132). Required for proper phospholipid bile formation (By similarity). Indirectly involved in cholesterol efflux activity from hepatocytes into the canalicular lumen in the presence of bile salts in an ATP-dependent manner (PubMed:24045840). Promotes biliary phospholipid secretion as canaliculi-containing vesicles from the canalicular plasma membrane (PubMed:28012258, PubMed:9366571). In cooperation with ATP8B1, functions to protect hepatocytes from the deleterious detergent activity of bile salts (PubMed:21820390). Does not confer multidrug resistance (By similarity)
- Specific Function
- ABC-type transporter activity
- Gene Name
- ABCB4
- Uniprot ID
- P21439
- Uniprot Name
- Phosphatidylcholine translocator ABCB4
- Molecular Weight
- 141521.845 Da
References
- Kakuda TN, Scholler-Gyure M, Hoetelmans RM: Pharmacokinetic interactions between etravirine and non-antiretroviral drugs. Clin Pharmacokinet. 2011 Jan;50(1):25-39. doi: 10.2165/11534740-000000000-00000. [Article]
- Scholler-Gyure M, Kakuda TN, Raoof A, De Smedt G, Hoetelmans RM: Clinical pharmacokinetics and pharmacodynamics of etravirine. Clin Pharmacokinet. 2009;48(9):561-74. doi: 10.2165/10895940-000000000-00000. [Article]
Drug created at March 19, 2008 16:32 / Updated at October 13, 2024 00:21