Dolutegravir
Identification
- Summary
Dolutegravir is an antiviral agent used for the treatment of HIV-1 infections in combination with other antiretroviral agents.
- Brand Names
- Dovato, Juluca, Tivicay, Triumeq
- Generic Name
- Dolutegravir
- DrugBank Accession Number
- DB08930
- Background
Dolutegravir is an HIV-1 integrase inhibitor that blocks the strand transfer step of the integration of the viral genome into the host cell (INSTI).1 The effect of this drug has no homology in human host cells, which gives it excellent tolerability and minimal toxicity.11 Dolutegravir was developed by ViiV Healthcare and FDA-approved on August 12, 2013.16 On November 21, 2017, dolutegravir, in combination with rilpivirine, was approved as part of the first complete treatment regimen with only two drugs for the treatment of adults with HIV-1 named Juluca.17
- Type
- Small Molecule
- Groups
- Approved
- Structure
- Weight
- Average: 419.3788
Monoisotopic: 419.129277143 - Chemical Formula
- C20H19F2N3O5
- Synonyms
- Dolutegravir
- External IDs
- GSK572
- S-349572
- S/GSK1349572
Pharmacology
- Indication
Dolutegravir is indicated in combination with other antiretroviral agents for the treatment of patients with HIV-1 infection that comply with the characteristics of being adults or children aged 12 years and older and present at least a weight of 40 kg.7 The FDA combination therapy approval of dolutegravir and rilpivirine is indicated for adults with HIV-1 infections whose virus is currently suppressed (< 50 copies/ml) on a stable regimen for at least six months, without history of treatment failure and no known substitutions associated to resistance to any of the two components of the therapy.17
Dolutegravir is also available in combination with lamivudine and abacavir for the treatment of adult and pediatric patients with HIV-1 who weigh ≥10kg.19
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 •••••••••••• ••••••••••• ••••••••• ••••••••• •••••••••••• •••••••• •• ••••• • ••• ••••••••• •••••• •••••••• ••••••••••••••• ••••••• ••••••• ••• •••••••••• Adjunct therapy in treatment of Human immunodeficiency virus type 1 (hiv-1) infection •••••••••••• ••••••••••• ••••••••• •••••••• •• ••••• • ••• ••••••••• ••••• ••••••• ••••••• ••• •••••••••• Adjunct therapy in treatment of Human immunodeficiency virus type 1 (hiv-1) infection •••••••••••• ••••• ••••••••• ••••• ••••••• ••••••• ••• •••••••••• Adjunct therapy in treatment of Human immunodeficiency virus type 1 (hiv-1) infection •••••••••••• ••••• ••••••••• ••••••••••• ••••••• ••••••• ••• •••••••••• Used in combination to treat Human immunodeficiency virus type 1 (hiv-1) infection Regimen in combination with: Rilpivirine (DB08864) •••••••••••• ••••• •• ••••••• •• ••••••••• •••••••• •••••• •••••••••••••• •••••••• ••••••••••••• •••••••••• •••••• ••• •••• •••• •• •••••• ••• ••• ••••••• ••••••• ••• •••••••••• - 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
HIV-1 infected subjects on dolutegravir monotherapy demonstrated rapid and dose-dependent reduction of antiviral activity with declines of HIV-1 RNA copies per ml. The antiviral response was maintained for 3 to 4 days after the last dose.3 The sustained response obtained in clinical trials indicates that dolutegravir has a tight binding and longer dissociative half-life providing it a high barrier to resistance.15 The combination therapy (ripivirine and dolutegravir) presented the same viral suppression found in previous three-drug therapies without integrase strand transfer inhibitor mutations or rilpivirine resistance.18
- Mechanism of action
Dolutegravir is an HIV-1 antiviral agent. It inhibits HIV integrase by binding to the active site and blocking the strand transfer step of retroviral DNA integration in the host cell. The strand transfer step is essential in the HIV replication cycle and results in the inhibition of viral activity. Dolutegravir has a mean EC50 value of 0.5 nM (0.21 ng/mL) to 2.1 nM (0.85 ng/mL) in peripheral blood mononuclear cells (PBMCs) and MT-4 cells.4
Target Actions Organism AIntegrase inhibitorHuman immunodeficiency virus 1 - Absorption
When 50 mg of dolutegravir once daily was orally administered to HIV-1 infected adults, the AUC, Cmax, and Cmin is 53.6 mcg h/mL, 3.67 mcg/mL, and 1.11 mcg/mL, respectively. The peak plasma concentration was observed 2 to 3 hours post-dose. Steady state is achieved within approximately 5 days with average accumulation ratios for AUC, Cmax, and C24h ranging from 1.2 to 1.5. When 50 mg once daily is given to pediatric patients (12 to < 18 years and weighing ≥40 kg) the Cmax, AUC, and C24 is 3.49 mcg/mL, 46 mcg.h/mL, and 0.90 mcg/mL respectively.1
- Volume of distribution
The administration of a dose of 50 mg of dolutegravir presents an apparent volume of distribution of 17.4 L. The median dolutegravir concentration in CSF was 18 ng/mL after 2 weeks of treatment.1
- Protein binding
Dolutegravir is highly protein bound to human plasma proteins reaching a percentage 98.9% of the administered dose.1
- Metabolism
Dolutegravir is highly metabolized through three main pathways and it forms no long-lived metabolites. The first pathway is defined by the glucuronidation by UGT1A1, the second pathway by carbon oxidation by CYP3A4 and the third pathway is what appears to be a sequential oxidative defluorination and glutathione conjugation. The main metabolite found in blood plasma is the ether glucuronide form (M2) and its chemical properties disrupt its ability to bind metal ions, therefore, it is inactive.12
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- Route of elimination
When a single oral dose of dolutegravir is given, nearly all complete dose is recovered in a proportion of 53% excreted unchanged in the feces and 31% excreted in urine. The renal eliminated recovered dose consists of ether glucuronide of dolutegravir (18.9%), a metabolite formed by oxidation at the benzylic carbon (3.0%), a hydrolytic N-dealkylation product (3.6%) and unchanged drug (< 1%).12
- Half-life
The half-life of dolutegravir is 14 hours.1
- Clearance
The apparent clearance rate of dultegravir is 1.0 L/h.Label
- 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
Data from an ongoing birth outcome surveillance study has identified an increased risk of neural tube defects when dolutegravir is administered at the time of conception. As defects related to the closure of the neural tube occur from conception through the first 6 weeks of gestation, embryos exposed to dolutegravir from the time of conception through the first 6 weeks of gestation are at potential risk.
Advise adolescents and adults of childbearing potential, including those actively trying to become pregnant, of the potential risk of neural tube defects with the use of TIVICAY and TIVICAY PD. Assess the risks and benefits of TIVICAY and TIVICAY PD and discuss with the patient to determine if an alternative treatment should be considered at the time of conception through the first trimester of pregnancy or if pregnancy is confirmed in the first trimester. A benefit-risk assessment should consider factors such as the feasibility of switching to another antiretroviral regimen, tolerability, ability to maintain viral suppression, and risk of HIV-1 transmission to the infant against the risk of neural tube defects associated with in-utero dolutegravir exposure during critical periods of fetal development [see Warnings and Precautions (5.3)].
There are insufficient human data on the use of dolutegravir during pregnancy to definitively assess a drug-associated risk for birth defects and miscarriage. The background risk for major birth defects for the indicated population is unknown. In the U.S. general population, the estimated background rate for major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.
In animal reproduction studies, no evidence of adverse developmental outcomes was observed with dolutegravir at systemic exposures (AUC) less than (rabbits) and approximately 27 times (rats) the exposure in humans at the maximum recommended human dose (MRHD) of TIVICAY (see Data).
There is no known specific treatment for an overdose with TIVICAY or TIVICAY PD. If an overdose occurs, the patient should be monitored, and standard supportive treatment applied as required. As dolutegravir is highly bound to plasma proteins, it is unlikely that it will be significantly removed by dialysis.
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs Browse all" title="About SNP Mediated Effects/ADRs" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">
Interacting Gene/Enzyme Allele name Genotype(s) Defining Change(s) Type(s) Description Details UDP-glucuronosyltransferase 1-1 UGT1A1*28 or UGT1A 7/7 Not Available extra TA in promoter Effect Directly Studied Poor drug metabolizer. Details UDP-glucuronosyltransferase 1-1 UGT1A1*6 Not Available G > A Effect Directly Studied The presence of this polymorphism in UGT1A1 is associated with reduction in dolutegravir metabolism. Details UDP-glucuronosyltransferase 1-1 UGT1A1*37 Not Available TA pair insertion Effect Directly Studied The presence of this polymorphism in UGT1A1 is associated with reduction in dolutegravir metabolism. Details
Interactions
- Drug Interactions Learn More" title="About Drug Interactions" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">
- 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 softwareAbemaciclib Abemaciclib may decrease the excretion rate of Dolutegravir which could result in a higher serum level. Abrocitinib The serum concentration of Dolutegravir can be increased when it is combined with Abrocitinib. Acamprosate The excretion of Acamprosate can be decreased when combined with Dolutegravir. Acyclovir The excretion of Acyclovir can be decreased when combined with Dolutegravir. Adagrasib The serum concentration of Dolutegravir can be increased when it is combined with Adagrasib. - Food Interactions
- Avoid multivalent ions. Cations should be separated from dolutegravir administration by 2 hours before and 6 hours after cation administration. Cations can be administered with dolutegravir if given with food.
- Avoid St. John's Wort.
- Take with or without food. Food, particularly high-fat meals, may increase the AUC, Cmax, and Tmax of dolutegravir.
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.
- Product Ingredients
Ingredient UNII CAS InChI Key Dolutegravir sodium 1Q1V9V5WYQ 1051375-19-9 UGWJRRXTMKRYNK-VSLILLSYSA-M - Product Images
- Brand Name Prescription Products
- Mixture Products
Name Ingredients Dosage Route Labeller Marketing Start Marketing End Region Image ACRIPTEGA Dolutegravir (50 MG) + Lamivudine (300 MG) + Tenofovir disoproxil fumarate (300 MG) Tablet, coated Oral บริษัท ซาย ฟาร์มา จำกัด จำกัด 2019-12-27 Not applicable Thailand Dovato Dolutegravir sodium (50 mg) + Lamivudine (300 mg) Tablet, film coated Oral Vii V Healthcare B.V. 2023-09-13 Not applicable EU Dovato Dolutegravir sodium (50 mg) + Lamivudine (300 mg) Tablet Oral ViiV Healthcare ULC 2019-09-09 Not applicable Canada DOVATO Dolutegravir (50 MG) + Lamivudine (300 MG) Tablet, film coated Oral Viiv Healthcare Bv 2019-12-21 Not applicable Italy Dovato Dolutegravir sodium (50 mg) + Lamivudine (300 mg) Tablet, film coated Oral Vii V Healthcare B.V. 2022-06-10 Not applicable EU
Categories
- ATC Codes
- J05AR27 — Lamivudine, tenofovir disoproxil and dolutegravir
- J05AR — Antivirals for treatment of HIV infections, combinations
- J05A — DIRECT ACTING ANTIVIRALS
- J05 — ANTIVIRALS FOR SYSTEMIC USE
- J — ANTIINFECTIVES FOR SYSTEMIC USE
- J05AJ — Integrase inhibitors
- J05A — DIRECT ACTING ANTIVIRALS
- J05 — ANTIVIRALS FOR SYSTEMIC USE
- J — ANTIINFECTIVES FOR SYSTEMIC USE
- J05AR — Antivirals for treatment of HIV infections, combinations
- J05A — DIRECT ACTING ANTIVIRALS
- J05 — ANTIVIRALS FOR SYSTEMIC USE
- J — ANTIINFECTIVES FOR SYSTEMIC USE
- J05AR — Antivirals for treatment of HIV infections, combinations
- J05A — DIRECT ACTING ANTIVIRALS
- J05 — ANTIVIRALS FOR SYSTEMIC USE
- J — ANTIINFECTIVES FOR SYSTEMIC USE
- Drug Categories
- Anti-HIV Agents
- Anti-Infective Agents
- Anti-Retroviral Agents
- Antiinfectives for Systemic Use
- Antiviral Agents
- Antivirals for Systemic Use
- Antivirals used in combination for the treatment of HIV infections
- BCRP/ABCG2 Substrates
- Direct Acting Antivirals
- Enzyme Inhibitors
- Heterocyclic Compounds, Fused-Ring
- HIV Integrase Inhibitors
- Human Immunodeficiency Virus Integrase Strand Transfer Inhibitor
- Integrase Inhibitors
- MATE 1 Inhibitors
- MATE inhibitors
- OAT1/SLC22A6 inhibitors
- OAT3/SLC22A8 Inhibitors
- OCT2 Inhibitors
- P-glycoprotein substrates
- UGT1A1 Substrates
- UGT1A3 substrates
- UGT1A9 Substrates
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as pyridinecarboxylic acids and derivatives. These are compounds containing a pyridine ring bearing a carboxylic acid group or a derivative thereof.
- Kingdom
- Organic compounds
- Super Class
- Organoheterocyclic compounds
- Class
- Pyridines and derivatives
- Sub Class
- Pyridinecarboxylic acids and derivatives
- Direct Parent
- Pyridinecarboxylic acids and derivatives
- Alternative Parents
- 2-heteroaryl carboxamides / Fluorobenzenes / Hydroxypyridines / 1,3-oxazinanes / Aryl fluorides / Vinylogous amides / Vinylogous acids / Tertiary carboxylic acid amides / Heteroaromatic compounds / Secondary carboxylic acid amides show 9 more
- Substituents
- 1,3-oxazinane / 2-heteroaryl carboxamide / Aromatic heteropolycyclic compound / Aryl fluoride / Aryl halide / Azacycle / Benzenoid / Carboxamide group / Carboxylic acid derivative / Cyclic ketone show 22 more
- Molecular Framework
- Aromatic heteropolycyclic compounds
- External Descriptors
- organofluorine compound, monocarboxylic acid amide, organic heterotricyclic compound (CHEBI:76010)
- Affected organisms
- Humans and other mammals
- Human Immunodeficiency Virus
Chemical Identifiers
- UNII
- DKO1W9H7M1
- CAS number
- 1051375-16-6
- InChI Key
- RHWKPHLQXYSBKR-BMIGLBTASA-N
- InChI
- InChI=1S/C20H19F2N3O5/c1-10-4-5-30-15-9-24-8-13(17(26)18(27)16(24)20(29)25(10)15)19(28)23-7-11-2-3-12(21)6-14(11)22/h2-3,6,8,10,15,27H,4-5,7,9H2,1H3,(H,23,28)/t10-,15+/m1/s1
- IUPAC Name
- (3S,7R)-N-[(2,4-difluorophenyl)methyl]-11-hydroxy-7-methyl-9,12-dioxo-4-oxa-1,8-diazatricyclo[8.4.0.0^{3,8}]tetradeca-10,13-diene-13-carboxamide
- SMILES
- [H][C@]12CN3C=C(C(=O)NCC4=CC=C(F)C=C4F)C(=O)C(O)=C3C(=O)N1[C@H](C)CCO2
References
- General References
- Min S, Song I, Borland J, Chen S, Lou Y, Fujiwara T, Piscitelli SC: Pharmacokinetics and safety of S/GSK1349572, a next-generation HIV integrase inhibitor, in healthy volunteers. Antimicrob Agents Chemother. 2010 Jan;54(1):254-8. doi: 10.1128/AAC.00842-09. Epub 2009 Nov 2. [Article]
- Lenz JC, Rockstroh JK: S/GSK1349572, a new integrase inhibitor for the treatment of HIV: promises and challenges. Expert Opin Investig Drugs. 2011 Apr;20(4):537-48. doi: 10.1517/13543784.2011.562189. Epub 2011 Mar 8. [Article]
- Min S, Sloan L, DeJesus E, Hawkins T, McCurdy L, Song I, Stroder R, Chen S, Underwood M, Fujiwara T, Piscitelli S, Lalezari J: Antiviral activity, safety, and pharmacokinetics/pharmacodynamics of dolutegravir as 10-day monotherapy in HIV-1-infected adults. AIDS. 2011 Sep 10;25(14):1737-45. doi: 10.1097/QAD.0b013e32834a1dd9. [Article]
- Hare S, Smith SJ, Metifiot M, Jaxa-Chamiec A, Pommier Y, Hughes SH, Cherepanov P: Structural and functional analyses of the second-generation integrase strand transfer inhibitor dolutegravir (S/GSK1349572). Mol Pharmacol. 2011 Oct;80(4):565-72. doi: 10.1124/mol.111.073189. Epub 2011 Jun 30. [Article]
- Katlama C, Murphy R: Dolutegravir for the treatment of HIV. Expert Opin Investig Drugs. 2012 Apr;21(4):523-30. doi: 10.1517/13543784.2012.661713. Epub 2012 Mar 2. [Article]
- Cahn P, Pozniak AL, Mingrone H, Shuldyakov A, Brites C, Andrade-Villanueva JF, Richmond G, Buendia CB, Fourie J, Ramgopal M, Hagins D, Felizarta F, Madruga J, Reuter T, Newman T, Small CB, Lombaard J, Grinsztejn B, Dorey D, Underwood M, Griffith S, Min S: Dolutegravir versus raltegravir in antiretroviral-experienced, integrase-inhibitor-naive adults with HIV: week 48 results from the randomised, double-blind, non-inferiority SAILING study. Lancet. 2013 Aug 24;382(9893):700-8. doi: 10.1016/S0140-6736(13)61221-0. Epub 2013 Jul 3. [Article]
- Authors unspecified: Dolutegravir (Tivicay) for HIV. Med Lett Drugs Ther. 2013 Sep 30;55(1426):77-9. [Article]
- Cottrell ML, Hadzic T, Kashuba AD: Clinical pharmacokinetic, pharmacodynamic and drug-interaction profile of the integrase inhibitor dolutegravir. Clin Pharmacokinet. 2013 Nov;52(11):981-94. doi: 10.1007/s40262-013-0093-2. [Article]
- Ballantyne AD, Perry CM: Dolutegravir: first global approval. Drugs. 2013 Sep;73(14):1627-37. doi: 10.1007/s40265-013-0121-4. [Article]
- Boyd MA, Donovan B: Antiretroviral therapy: dolutegravir sets SAIL(ING). Lancet. 2013 Aug 24;382(9893):664-6. doi: 10.1016/S0140-6736(13)61456-7. Epub 2013 Jul 3. [Article]
- Dow DE, Bartlett JA: Dolutegravir, the Second-Generation of Integrase Strand Transfer Inhibitors (INSTIs) for the Treatment of HIV. Infect Dis Ther. 2014 Dec;3(2):83-102. doi: 10.1007/s40121-014-0029-7. Epub 2014 Jun 24. [Article]
- Castellino S, Moss L, Wagner D, Borland J, Song I, Chen S, Lou Y, Min SS, Goljer I, Culp A, Piscitelli SC, Savina PM: Metabolism, excretion, and mass balance of the HIV-1 integrase inhibitor dolutegravir in humans. Antimicrob Agents Chemother. 2013 Aug;57(8):3536-46. doi: 10.1128/AAC.00292-13. Epub 2013 May 13. [Article]
- Elzi L, Erb S, Furrer H, Cavassini M, Calmy A, Vernazza P, Gunthard H, Bernasconi E, Battegay M: Adverse events of raltegravir and dolutegravir. AIDS. 2017 Aug 24;31(13):1853-1858. doi: 10.1097/QAD.0000000000001590. [Article]
- Adams JL, Greener BN, Kashuba AD: Pharmacology of HIV integrase inhibitors. Curr Opin HIV AIDS. 2012 Sep;7(5):390-400. doi: 10.1097/COH.0b013e328356e91c. [Article]
- DeAnda F, Hightower KE, Nolte RT, Hattori K, Yoshinaga T, Kawasuji T, Underwood MR: Dolutegravir interactions with HIV-1 integrase-DNA: structural rationale for drug resistance and dissociation kinetics. PLoS One. 2013 Oct 16;8(10):e77448. doi: 10.1371/journal.pone.0077448. eCollection 2013. [Article]
- ViiV Healthcare News [Link]
- FDA News and Events [Link]
- Johnson & Johnson News: Janssen Announces U.S. FDA Approval of First and Only Complete, Single-Pill, Two-Drug Regimen, JULUCA® (Dolutegravir and Rilpivirine), for the Treatment of HIV-1 Infection [Link]
- FDA Approved Drug Products: Triumeq/Triumeq PD (abacavir, dolutegravir, and lamivudine) for oral administration [Link]
- FDA Approved Drug Products: TIVICAY (dolutegravir) tablets, for oral use or oral suspension [Link]
- FDA Approved Drug Products: JULUCA (dolutegravir and rilpivirine tablets), for oral use [Link]
- FDA Approved Drug Products: DOVATO (dolutegravir and lamivudine) tablets, for oral use [Link]
- External Links
- KEGG Drug
- D10066
- PubChem Compound
- 54726191
- PubChem Substance
- 175427161
- ChemSpider
- 25051637
- BindingDB
- 50062551
- 1433868
- ChEBI
- 76010
- ChEMBL
- CHEMBL1229211
- ZINC
- ZINC000058581064
- PharmGKB
- PA166114961
- PDBe Ligand
- DLU
- Drugs.com
- Drugs.com Drug Page
- Wikipedia
- Dolutegravir
- PDB Entries
- 3s3m / 3s3n / 3s3o / 6rwn / 6u8q / 6vdk / 8fn7 / 8fnd / 8fng / 8fnh … show 6 more
- FDA label
- Download (332 KB)
- MSDS
- Download (61.6 KB)
Clinical Trials
- Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">
Phase Status Purpose Conditions Count 4 Active Not Recruiting Basic Science ART / Contraception / Human Immunodeficiency Virus (HIV) Infections 1 4 Active Not Recruiting Treatment Fatty Liver Disease / Human Immunodeficiency Virus (HIV) Infections 1 4 Active Not Recruiting Treatment Human Immunodeficiency Virus (HIV) Infections 4 4 Active Not Recruiting Treatment Human Immunodeficiency Virus (HIV) Infections / Human Immunodeficiency Virus Type 1 (HIV-1) Infection 1 4 Active Not Recruiting Treatment Human Immunodeficiency Virus (HIV) Infections / Tuberculosis (TB) 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Tablet, for suspension Oral 10 mg/1 Tablet, film coated Oral 52.6 MG Tablet Oral Tablet Oral 10 mg Tablet Oral 10.500 mg Tablet Oral 25 mg Tablet Oral 50 mg Tablet, film coated Oral 10 mg/1 Tablet, film coated Oral 25 mg/1 Tablet, film coated Oral 50 mg/1 Tablet, for suspension Oral 5 mg Tablet, film coated Oral Tablet Oral 5.260 mg Tablet, for suspension Oral 5 mg/1 Tablet, film coated Oral 50 mg Tablet Oral Tablet, film coated Oral Tablet, coated Oral Kit; tablet, film coated Oral Tablet, film coated Oral 10 mg Tablet, film coated Oral 25 mg Tablet, coated Oral 50 mg - Prices
- Not Available
- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US9242986 Yes 2016-01-26 2030-06-08 US US5905082 Yes 1999-05-18 2016-11-18 US US6294540 Yes 2001-09-25 2018-11-14 US US6417191 Yes 2002-07-09 2016-09-28 US US7125879 No 2006-10-24 2022-08-09 US US6838464 No 2005-01-04 2021-02-26 US US8080551 No 2011-12-20 2023-04-11 US US8101629 No 2012-01-24 2022-08-09 US US7067522 No 2006-06-27 2019-12-20 US US8129385 Yes 2012-03-06 2028-04-05 US US10426780 No 2019-10-01 2031-01-24 US US11234985 No 2011-01-24 2031-01-24 US
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 190-193ºC MSDS water solubility Slightly soluble FDA label logP 2.2 MSDS pKa 8.2 MSDS - Predicted Properties
Property Value Source Water Solubility 0.0922 mg/mL ALOGPS logP 0.98 ALOGPS logP 1.1 Chemaxon logS -3.7 ALOGPS pKa (Strongest Acidic) 10.1 Chemaxon pKa (Strongest Basic) -0.51 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 6 Chemaxon Hydrogen Donor Count 2 Chemaxon Polar Surface Area 99.18 Å2 Chemaxon Rotatable Bond Count 3 Chemaxon Refractivity 102.77 m3·mol-1 Chemaxon Polarizability 40 Å3 Chemaxon Number of Rings 4 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes 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
Spectrum Spectrum Type Splash Key Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS splash10-00di-0030900000-4534f34038330703cccf Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS splash10-0002-0091200000-6a440597a193c50eaf0b Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS splash10-004i-0090100000-0ca312dc57b4531a170b Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS splash10-016v-4298300000-ab5e8123f8bbf56aa049 Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS splash10-0umi-0493100000-cfb28698b53af2ff903b Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS splash10-00kp-9647100000-b74e91a03fa736ca4181 Predicted 1H NMR Spectrum 1D NMR Not Applicable Predicted 13C NMR Spectrum 1D NMR Not Applicable - Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 203.42375 predictedDeepCCS 1.0 (2019) [M+H]+ 205.78175 predictedDeepCCS 1.0 (2019) [M+Na]+ 212.40889 predictedDeepCCS 1.0 (2019)
Targets
![](https://go.drugbank.com/assets/locked/DrugTargets2-682eb846d210ae4bf33ca03febccfb57bb1c61318e699b729e5df4dfab2c5b67.png)
- Kind
- Protein
- Organism
- Human immunodeficiency virus 1
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Zinc ion binding
- Specific Function
- Not Available
- Gene Name
- pol
- Uniprot ID
- Q7ZJM1
- Uniprot Name
- Integrase
- Molecular Weight
- 32226.645 Da
References
- Hare S, Smith SJ, Metifiot M, Jaxa-Chamiec A, Pommier Y, Hughes SH, Cherepanov P: Structural and functional analyses of the second-generation integrase strand transfer inhibitor dolutegravir (S/GSK1349572). Mol Pharmacol. 2011 Oct;80(4):565-72. doi: 10.1124/mol.111.073189. Epub 2011 Jun 30. [Article]
- Waki K, Sugawara Y: Implications of integrase inhibitors for HIV-infected transplantation recipients: raltegravir and dolutegravir (S/GSK 1349572). Biosci Trends. 2011;5(5):189-91. [Article]
- Underwood MR, Johns BA, Sato A, Martin JN, Deeks SG, Fujiwara T: The activity of the integrase inhibitor dolutegravir against HIV-1 variants isolated from raltegravir-treated adults. J Acquir Immune Defic Syndr. 2012 Nov 1;61(3):297-301. doi: 10.1097/QAI.0b013e31826bfd02. [Article]
- Dooley KE, Sayre P, Borland J, Purdy E, Chen S, Song I, Peppercorn A, Everts S, Piscitelli S, Flexner C: Safety, tolerability, and pharmacokinetics of the HIV integrase inhibitor dolutegravir given twice daily with rifampin or once daily with rifabutin: results of a phase 1 study among healthy subjects. J Acquir Immune Defic Syndr. 2013 Jan 1;62(1):21-7. doi: 10.1097/QAI.0b013e318276cda9. [Article]
- Cottrell ML, Hadzic T, Kashuba AD: Clinical pharmacokinetic, pharmacodynamic and drug-interaction profile of the integrase inhibitor dolutegravir. Clin Pharmacokinet. 2013 Nov;52(11):981-94. doi: 10.1007/s40262-013-0093-2. [Article]
- Rathbun RC, Lockhart SM, Miller MM, Liedtke MD: Dolutegravir, a second-generation integrase inhibitor for the treatment of HIV-1 infection. Ann Pharmacother. 2014 Mar;48(3):395-403. doi: 10.1177/1060028013513558. Epub 2013 Nov 19. [Article]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Substrate
- General Function
- Steroid binding
- Specific Function
- UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isoform glucuronidates bilirubin IX-alpha to form both the...
- Gene Name
- UGT1A1
- Uniprot ID
- P22309
- Uniprot Name
- UDP-glucuronosyltransferase 1-1
- Molecular Weight
- 59590.91 Da
References
- FDA Approved Drug Products: TIVICAY (dolutegravir) tablets, for oral use or oral suspension [Link]
- Kind
- Protein group
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Substrate
- General Function
- Vitamin d3 25-hydroxylase activity
- Specific Function
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Components:
Name | UniProt ID |
---|---|
Cytochrome P450 3A4 | P08684 |
Cytochrome P450 3A43 | Q9HB55 |
Cytochrome P450 3A5 | P20815 |
Cytochrome P450 3A7 | P24462 |
References
- FDA Approved Drug Products: TIVICAY (dolutegravir) tablets, for oral use or oral suspension [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Substrate
- General Function
- Retinoic acid binding
- Specific Function
- UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. Isoform 2 lacks transferase activity but acts as a negative reg...
- Gene Name
- UGT1A3
- Uniprot ID
- P35503
- Uniprot Name
- UDP-glucuronosyltransferase 1-3
- Molecular Weight
- 60337.835 Da
References
- FDA Approved Drug Products: TIVICAY (dolutegravir) tablets, for oral use or oral suspension [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Substrate
- General Function
- Retinoic acid binding
- Specific Function
- UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isoform has specificity for phenols. Isoform 2 lacks trans...
- Gene Name
- UGT1A9
- Uniprot ID
- O60656
- Uniprot Name
- UDP-glucuronosyltransferase 1-9
- Molecular Weight
- 59940.495 Da
References
- FDA Approved Drug Products: TIVICAY (dolutegravir) tablets, for oral use or oral suspension [Link]
Carriers
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Binder
- General Function
- Toxic substance binding
- Specific Function
- Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloid...
- Gene Name
- ALB
- Uniprot ID
- P02768
- Uniprot Name
- Serum albumin
- Molecular Weight
- 69365.94 Da
References
- Gele T, Gouget H, Furlan V, Becker PH, Taburet AM, Lambotte O, Barrail-Tran A: Characteristics of Dolutegravir and Bictegravir Plasma Protein Binding: a First Approach for the Study of Pharmacologic Sanctuaries. Antimicrob Agents Chemother. 2020 Oct 20;64(11). pii: AAC.00895-20. doi: 10.1128/AAC.00895-20. Print 2020 Oct 20. [Article]
- Kind
- Protein group
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Binder
- General Function
- Not Available
- Specific Function
- Functions as transport protein in the blood stream. Binds various ligands in the interior of its beta-barrel domain. Also binds synthetic drugs and influences their distribution and availability in...
Components:
References
- Gele T, Gouget H, Furlan V, Becker PH, Taburet AM, Lambotte O, Barrail-Tran A: Characteristics of Dolutegravir and Bictegravir Plasma Protein Binding: a First Approach for the Study of Pharmacologic Sanctuaries. Antimicrob Agents Chemother. 2020 Oct 20;64(11). pii: AAC.00895-20. doi: 10.1128/AAC.00895-20. Print 2020 Oct 20. [Article]
Transporters
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Inhibitor
- General Function
- Quaternary ammonium group transmembrane transporter activity
- Specific Function
- Mediates tubular uptake of organic compounds from circulation. Mediates the influx of agmatine, dopamine, noradrenaline (norepinephrine), serotonin, choline, famotidine, ranitidine, histamin, creat...
- Gene Name
- SLC22A2
- Uniprot ID
- O15244
- Uniprot Name
- Solute carrier family 22 member 2
- Molecular Weight
- 62579.99 Da
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Substrate
- General Function
- Xenobiotic-transporting atpase activity
- Specific Function
- High-capacity urate exporter functioning in both renal and extrarenal urate excretion. Plays a role in porphyrin homeostasis as it is able to mediates the export of protoporhyrin IX (PPIX) both fro...
- Gene Name
- ABCG2
- Uniprot ID
- Q9UNQ0
- Uniprot Name
- ATP-binding cassette sub-family G member 2
- Molecular Weight
- 72313.47 Da
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Inhibitor
- General Function
- Sodium-independent organic anion transmembrane transporter activity
- Specific Function
- Involved in the renal elimination of endogenous and exogenous organic anions. Functions as organic anion exchanger when the uptake of one molecule of organic anion is coupled with an efflux of one ...
- Gene Name
- SLC22A6
- Uniprot ID
- Q4U2R8
- Uniprot Name
- Solute carrier family 22 member 6
- Molecular Weight
- 61815.78 Da
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Inhibitor
- General Function
- Sodium-independent organic anion transmembrane transporter activity
- Specific Function
- Plays an important role in the excretion/detoxification of endogenous and exogenous organic anions, especially from the brain and kidney. Involved in the transport basolateral of steviol, fexofenad...
- Gene Name
- SLC22A8
- Uniprot ID
- Q8TCC7
- Uniprot Name
- Solute carrier family 22 member 8
- Molecular Weight
- 59855.585 Da
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Substrate
- General Function
- Xenobiotic-transporting atpase activity
- Specific Function
- Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
- Gene Name
- ABCB1
- Uniprot ID
- P08183
- Uniprot Name
- Multidrug resistance protein 1
- Molecular Weight
- 141477.255 Da
References
- Adams JL, Greener BN, Kashuba AD: Pharmacology of HIV integrase inhibitors. Curr Opin HIV AIDS. 2012 Sep;7(5):390-400. doi: 10.1097/COH.0b013e328356e91c. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Inhibitor
- General Function
- Monovalent cation:proton antiporter activity
- Specific Function
- Solute transporter for tetraethylammonium (TEA), 1-methyl-4-phenylpyridinium (MPP), cimetidine, N-methylnicotinamide (NMN), metformin, creatinine, guanidine, procainamide, topotecan, estrone sulfat...
- Gene Name
- SLC47A1
- Uniprot ID
- Q96FL8
- Uniprot Name
- Multidrug and toxin extrusion protein 1
- Molecular Weight
- 61921.585 Da
Drug created at November 11, 2013 21:17 / Updated at December 22, 2023 19:51