Elvitegravir (GS-9137; JTK-303; D06677) inhibits DNA strand transfer, which prevents HIV-1 cDNA integration. Elvitegravir exhibits strong anti-HIV properties against both drug-resistant clinical isolates and wild-type strains. Fascinatingly, elevategravir also demonstrates antiviral action against the simian immunodeficiency virus (SIV) and the murine leukemia virus (MLV). Three laboratory strains of HIV were effectively inhibited by elvitegravir, with EC50 values ranging from subnanomolar to nanomolar. Subsequently, Elvitegravir's efficacy was assessed in comparison to clinical isolates of wild-type HIV-1 subtypes. All HIV-1 subtypes examined with antiviral EC50s ranging from 0.1 to 1.26 nM are inhibited by elevategravir in terms of replication. Additionally, both elvitegravir and the control IN inhibitor drug L-870,810 prevented the replication of HIV-1 clinical isolates with genotypes linked to PI resistance, NRTI, and NNRTI. The MTT colorimetric test was also used to assess the cytotoxicity of these inhibitors. The average values of L-870,810 and Elvitegravir that reduced target cell viability by 50% in PBMC derived from three different donors were 2.7±0.6 μM and 4.6±0.5 μM, respectively. Elvitegravir thus suppresses a variety of HIV strains, including clinical isolates with numerous alterations linked to resistance to presently licensed antiretroviral medications and a number of HIV-1 subtypes [1].

Absorption, Distribution and Excretion
Following oral administration of elvitegravir and ritonavir with food, in HIV-1 infected subjects, peak elvitegravir plasma concentrations were observed approximately 4 hours post-dose.
Following oral administration of [14C]elvitegravir/ritonavir, 94.8% of the dose was recovered in feces, while 6.7% was recovered in urine as metabolites.

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Metabolism / Metabolites
Elvitegravir undergoes primarily oxidative metabolism via CYP3A, and is secondarily glucuronidated via UGT1A1/3 enzymes. Metabolites are found in the plasma at very low concentrations, displayed considerably lower anti-HIV activity, and did not contribute to the overall antiviral activity of elvitegravir.

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Biological Half-Life
The median terminal plasma half-life following administration of elvitegravir and ritonavir was approximately 8.7 hours.

Effects During Pregnancy and Lactation
◉ Summary of Use during Lactation
No published information is available on the use of elvitegravir during breastfeeding. An alternate agent may be preferred. Achieving and maintaining viral suppression with antiretroviral therapy decreases breastfeeding transmission risk to less than 1%, but not zero. Individuals with HIV who are on antiretroviral therapy with a sustained undetectable viral load and who choose to breastfeed should be supported in this decision. If a viral load is not suppressed, banked pasteurized donor milk or formula is recommended.
◉ Effects in Breastfed Infants
Relevant published information was not found as of the revision date.
◉ Effects on Lactation and Breastmilk
Gynecomastia has been reported among men receiving highly active antiretroviral therapy. Gynecomastia is unilateral initially, but progresses to bilateral in about half of cases. No alterations in serum prolactin were noted and spontaneous resolution usually occurred within one year, even with continuation of the regimen. Some case reports and in vitro studies have suggested that protease inhibitors might cause hyperprolactinemia and galactorrhea in some male patients, although this has been disputed. The relevance of these findings to nursing mothers is not known. The prolactin level in a mother with established lactation may not affect her ability to breastfeed.

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Protein Binding
Elvitegravir is 98–99% bound to human plasma proteins

[1]. Shimura K, et al. Broad antiretroviral activity and resistance profile of the novel human immunodeficiency virus integrase inhibitor elvitegravir (JTK-303/GS-9137). J Virol. 2008 Jan;82(2):764-74

Elvitegravir is a quinolinemonocarboxylic acid that is 7-methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid substited at position 1 by a 1-hydroxy-3-methylbutan-2-yl group and at position 6 by a 3-chloro-2-fluorobenzyl group (the S-enantiomer). It is used in combination therapy for the treatment of HIV-1 infection. It has a role as a HIV-1 integrase inhibitor. It is a quinolinemonocarboxylic acid, an organofluorine compound, an aromatic ether, a quinolone and a member of monochlorobenzenes.
Elvitegravir is a human immunodeficiency virus type 1 (HIV-1) integrase strand transfer inhibitor (INSTI) used for the treatment of HIV-1 infection in antiretroviral treatment-experienced adults. Because integrase is necessary for viral replication, inhibition prevents the integration of HIV-1 DNA into the host genome and thereby blocks the formation of the HIV-1 provirus and resulting propagation of the viral infection. Although available as a single dose tablet, elvitegravir must be used in combination with an HIV protease inhibitor coadministered with ritonavir and another antiretroviral drug. Elvitegravir was first licensed from Japan Tobacco in 2008 and developed by Gilead Sciences. It was FDA approved on August 27, 2012. On September 24, 2014, the FDA approved the single pill form of elvitegravir.
Elvitegravir is a Human Immunodeficiency Virus Integrase Strand Transfer Inhibitor. The mechanism of action of elvitegravir is as a HIV Integrase Inhibitor, and Cytochrome P450 2C9 Inducer.
Elvitegravir is a modified quinolone antibiotic with activity against human immunodeficiency virus 1. Elvitegravir is an inhibitor of viral integrase and retains activity against integrase mutants that are resistant to Raltegravir.
See also: ... View More ...

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Drug Indication
Elvitegravir in combination with an HIV protease inhibitor coadministered with ritonavir and with other antiretroviral drug(s) is indicated for the treatment of HIV-1 infection in antiretroviral treatment-experienced adults.
FDA Label
Vitekta co-administered with a ritonavir-boosted protease inhibitor and with other antiretroviral agents, is indicated for the treatment of human-immunodeficiency-virus-1 (HIV-1) infection in adults who are infected with HIV-1 without known mutations associated with resistance to elvitegravir.
Treatment of human immunodeficiency virus (HIV-1) infection

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Mechanism of Action
Elvitegravir is an HIV-1 integrase strand transfer inhibitor (INSTI). Integrase is an HIV-1 encoded enzyme that is required for viral replication. Inhibition of integrase prevents the integration of HIV-1 DNA into host genomic DNA, blocking the formation of the HIV-1 provirus and propagation of the viral infection. Elvitegravir does not inhibit human topoisomerases I or II.

C23H23CLFNO5

447.88

447.124

697761-98-1

Elvitegravir-d8

5277135

White to off-white solid powder

1.4±0.1 g/cm3

623.6±55.0 °C at 760 mmHg

93-96°C

330.9±31.5 °C

0.0±1.9 mmHg at 25°C

1.603

4.29

2

7

7

31

702

1

ClC1=C([H])C([H])=C([H])C(=C1F)C([H])([H])C1C(=C([H])C2=C(C=1[H])C(C(C(=O)O[H])=C([H])N2[C@]([H])(C([H])([H])O[H])C([H])(C([H])([H])[H])C([H])([H])[H])=O)OC([H])([H])[H]

JUZYLCPPVHEVSV-LJQANCHMSA-N

InChI=1S/C23H23ClFNO5/c1-12(2)19(11-27)26-10-16(23(29)30)22(28)15-8-14(20(31-3)9-18(15)26)7-13-5-4-6-17(24)21(13)25/h4-6,8-10,12,19,27H,7,11H2,1-3H3,(H,29,30)/t19-/m1/s1

InChI=1S/C19H17N5O2.2CH4O3S/c20-17(21)14-2-1-13-10-16(8-5-12(13)9-1(4)26-18(25)11-3-6-15(7-4-11)24-19(22)23;2*1-5(2,3)4/h1-10H,(H3,20,21)(H4,22,23,24);2*1H3,(H,2,3,4

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Solubility in Formulation 1: 2.5 mg/mL (5.58 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.08 mg/mL (4.64 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 3: ≥ 2.08 mg/mL (4.64 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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 (Please use freshly prepared in vivo formulations for optimal results.)