Chemical Property of Cobicistat
Chemical Property:
- Boiling Point:974.526 °C at 760 mmHg
- PKA:11.86±0.46(Predicted)
- Flash Point:543.174 °C
- PSA：194.50000
- Density:1.229 g/cm3
- LogP:7.11130
- Storage Temp.:Hygroscopic, Refrigerator, under inert atmosphere
- Solubility.:Chloroform (Slightly), DMSO (Slightly), Ethyl Acetate (Slightly), Methanol (Slig
- Purity/Quality:
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99%, *data from raw suppliers
Cobicistat-d8 *data from reagent suppliers
Safty Information:
- Pictogram(s):
- Hazard Codes:
- MSDS Files:
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SDS file from LookChem
Useful:
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Description
Cobicistat (GS-9350) is a potent and selective inhibitor of CYP3A with IC50 of 30-285 nM. Cobicistat, a selective, mechanism-based CYP3A inhibitor, was
discovered and developed by Gilead Sciences, Inc. In 2013,
European Medicines Agency (EMA) approved cobicistat (Tybost)
for the treatment of HIV-1 infection in combination with protease
inhibitors (PIs) atazanavir or darunavir. Interestingly, cobicistat
does not interact with HIV directly, but instead serves as a
pharmacokinetic enhancer to boost the anti-HIV effect of atazanavir
or darunavir through blockade of CYP3A. Cobicistat slows
CYP-mediated metabolism of atazanavir and darunavir, resulting
in prolonged systemic exposure of the drug(s). Cobicistat is also
available as part of a fixed-dose combination tablet (Stribild) of
four additional drugs with CYP3A liabilities (elvitegravir, cobicistat,
emtricitabine and tenofovir disoproxil fumarate), which was
approved in U.S. in 2012, and subsequently approved in Europe and Japan in 2013.
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Uses
Cobicistat is a HIV protease inhibitor and have been coadministered with low-dose ritonavir (R535000) as a pharmacoenhancer, significantly increasing their plasma concentrations. Isotope labelled analogue of Cobicistat (C633150), a HIV protease inhibitor and have been coadministered with low-dose ritonavir (R535000) as a pharmacoenhancer, significantly increasing their plasma
concentrations. Antiretroviral;Labeled Cobicistat, intended for use as an internal standard for the quantification of Cobicistat by GC- or LC-mass spectrometry.
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Clinical Use
Pharmacokinetic enhancer used to increase the effect of
atazanavir and darunavir
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Drug interactions
Potentially hazardous interactions with other drugsAlpha-blockers: concentration of alfuzosin possibly
increased - avoid.
Anti-arrhythmics: concentration of amiodarone
possibly increased - avoid.
Antibacterials: concentration reduced by rifabutin
and rifampicin - adjust cobicistat dose, avoid with
rifampicin.
Anticoagulants: avoid with apixaban; anticoagulant
effect of rivaroxaban possibly enhanced - avoid.
Antidepressants: concentration possibly reduced by
St John’s wort - avoid.
Antiepileptics: concentration of cobicistat
possibly reduced by carbamazepine, fosphenytoin
phenobarbital, phenytoin and primidone - avoid.
Antifungals: concentration of itraconazole and
ketoconazole possibly increased - reduce antifungal
dose.
Antipsychotics: concentration of lurasidone and
pimozide possibly increased - avoid.
Antivirals: concentration of daclatasvir and
maraviroc possibly increased - reduce daclatasvir
and maraviroc dose; avoid with dasabuvir, nevirapine,
ombitasvir, paritaprevir, ritonavir and simeprevir;
concentration of elbasvir and grazoprevir increased -
avoid; concentration of olaparib possibly increased -
avoid or reduce olaparib dose; concentration of both
drugs reduced with tipranavir - avoid.
Anxiolytics: avoid with oral midazolam.
Avanafil: concentration of avanafil possibly increased
- avoid.
Bosentan: avoid concomitant use.
Cardiac glycosides: concentration of digoxin possibly
increased - reduce initial dose of digoxin.
Corticosteroids: concentration of corticosteroids
possibly increased avoid or use with caution.
Cytotoxics: concentration of ibrutinib possibly
increased - reduce ibrutinib dose; concentration of
olaparib possibly increased - avoid or reduce dose of
olaparib.
Domperidone: possible increased risk of ventricular
arrhythmias - avoid.
Ergot alkaloids: concentration of ergot alkaloids
possibly increased - avoid.
Immunosuppression: concentration of ciclosporin,
sirolimus and tacrolimus possibly increased.
Lipid-lowering drugs: concentration of atorvastatin
possibly increased - reduce atorvastatin dose; avoid
with simvastatin.
Oestrogens: metabolism of oestrogens accelerated,
reduced contraceptive effect - avoid or use with
caution. Salmeterol: avoid concomitant use.
Sildenafil: concentration of sildenafil possibly
increased - avoid sildenafil for pulmonary arterial
hypertension, reduce dose for erectile dysfunction.
Tadalafil: concentration of tadalafil possibly
increased - reduce dose of tadalafil.
Vardenafil: concentration of vardenafil possibly
increased - reduce dose of vardenafil.
