(1,3-thiazol-5-yl) methyl (5S, 8R, 11R) -8,11-dibenzyl-2-methyl-5-[2 – (morpholin-4-yl) ethyl] -1 – [2 – (propan-2-yl) -1,3-thiazol-4-yl] -3,6-dioxo-2 ,4,7,12-tetraazatridecan-13-oate
cytochrome P450 3A4 (CYP3A4) inhibitor
Tybost Facilitates Once-Daily Dosing of the Protease Inhibitors Atazanavir and Darunavir –
FOSTER CITY, Calif.–(BUSINESS WIRE)–Sep. 25, 2013– Gilead Sciences, Inc. (Nasdaq: GILD) today announced that the European Commission has granted marketing authorization for once-daily TybostTM (cobicistat 150 mg tablets), a pharmacokinetic enhancer that boosts blood levels of certain HIV medicines. Tybost is indicated as a boosting agent for the HIV protease inhibitors atazanavir 300 mg once daily and darunavir 800 mg once daily as part of antiretroviral combination therapy in adults with HIV-1 infection. Today’s approval allows for the marketing of Tybost in all 28 countries of the European Union (EU).
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Cobicistat (formerly GS-9350) is a licensed drug for use in the treatment of infection with the human immunodeficiency virus (HIV).
Like ritonavir (Norvir), cobicistat is of interest not for its anti-HIV properties, but rather its ability to inhibit liver enzymes that metabolize other medications used to treat HIV, notablyelvitegravir, an HIV integrase inhibitor currently under investigation itself. By combining cobicistat with elvitegravir, higher concentrations of elvitgravir are achieved in the body with lower dosing, theoretically enhancing elvitgravir’s viral suppression while diminishing its adverse side-effects. In contrast with ritonavir, the only currently approved booster, cobicistat has no anti-HIV activity of its own.
Cobicistat is a component of the four-drug, fixed-dose combination HIV treatmentelvitegravir/cobicistat/emtricitabine/tenofovir (known as the “Quad Pill” or Stribild). The Quad Pill/Stribild was approved by the FDA in August 2012 for use in the United States and is owned by Gilead Sciences.
Cobicistat is a potent inhibitor of cytochrome P450 3A enzymes, including the importantCYP3A4 subtype. It also inhibits intestinal transport proteins, increasing the overall absorption of several HIV medications, including atazanavir, darunavir and tenofovir alafenamide fumarate.
- Highleyman, L. Elvitegravir “Quad” Single-tablet Regimen Shows Continued HIV Suppression at 48 Weeks. HIV and Hepatitis.com
- R Elion, J Gathe, B Rashbaum, and others. The Single-Tablet Regimen of Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Disoproxil Fumarate (EVG/COBI/FTC/TDF; Quad) Maintains a High Rate of Virologic Suppression, and Cobicistat (COBI) is an Effective Pharmacoenhancer Through 48 Weeks. 50th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC 2010). Boston, September 12–15, 2010.
- Lepist, E. -I.; Phan, T. K.; Roy, A.; Tong, L.; MacLennan, K.; Murray, B.; Ray, A. S. (2012). “Cobicistat Boosts the Intestinal Absorption of Transport Substrates, Including HIV Protease Inhibitors and GS-7340, in Vitro”. Antimicrobial Agents and Chemotherapy 56 (10): 5409–5413. doi:10.1128/AAC.01089-12. PMC 3457391. PMID 22850510.
Quad ® laboratoryGilead Sciences , which funded the two clinical trials that have been published, containing a mixture of three active ingredients:tenofovir ,emtricitabine and a new active antiretroviral elvitegravir , also a CYP3A4 inhibitor called cobicistat.
The chemical structures of some of these HCV inhibitors as reported by numerous sources are provided below:
GS-333126 (GS-9190 or tegobuvir)
Mericitabine (R-4048 or RG7128 or R7128)
 BMS-791 As used herein, BMS-
791325 may also be
See also publications at http://wwwl .easl.eu/easl201 l/program/’Posters/Abstract680.htm; and http://clinicaltrials.gov/show/NCT00664625. For GS-5885, see publications at http://www.natap.org/201 l/EASL/EASL_68.htm; http://wwwl .easl.eu/easl2011/program/Posters/Abstractl 097.htm; and http://clinicaltrials.gov/ct2/show/NCT01353248.