Abstract
Purpose
This article reviews the clinical pharmacology, pharmacodynamic and pharmacokinetic
(PK) properties, clinical efficacy and tolerability, drug interactions, and dosing
and administration of cobicistat.
Methods
Searches of MEDLINE and International Pharmaceutical Abstracts from 1964 to February
2015 were conducted using the search terms cobicistat and GS-9350. Relevant information was extracted from the identified clinical trials and review
articles. Abstracts from the Conference on Retroviruses and Opportunistic Infections
(2014–2015) and the Interscience Conference on Antimicrobial Agents and Chemotherapy
(2013–2014) were also searched.
Findings
Cobicistat is a PK enhancer lacking antiviral activity that, via selective cytochrome
P-450 (CYP) 3A inhibition, inhibits the metabolism of certain antiretroviral medications
and is used for prolonging their effect. Cobicistat has been studied as a booster
of elvitegravir, a second-generation integrase inhibitor, and of the protease inhibitors
atazanavir and darunavir. Data on its clinical efficacy and tolerability have been
presented in 2 Phase II trials and in 9 Phase III trials, which reported durable efficacy
in terms of achievement of sustained suppression of HIV-1 RNA levels to <50 copies/mL
for at least 48 weeks. Cobicistat was generally well-tolerated in these studies. Cobicistat
may increase serum creatinine levels via the inhibition of proximal renal tubular
cell transporters and thus reduce estimated glomerular filtration rate, although it
does not appear to affect actual glomerular filtration rate. Given the potent CYP3A
inhibition by cobicistat, its coadministration with drugs metabolized by CYP3A may
result in increased plasma concentrations of such agents. Moreover, as cobicistat
is metabolized predominantly by CYP3A, plasma concentrations may increase or decrease
on coadministration with CYP3A inhibitors or inducers, respectively.
Implications
With potent durability through 48 weeks, a tolerability profile comparable to other
first- and second-line antiretroviral therapies, and a convenient dosing schedule
with low daily pill burden in fixed-dose combination tablets, cobicistat is a potential
addition to the management of HIV infection as a PK enhancer. However, the effects
of cobicistat on serum creatinine and its considerable drug-interaction potential
may warrant additional monitoring.
Key words
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Article Info
Publication History
Published online: August 25, 2015
Accepted:
July 30,
2015
Identification
Copyright
© 2015 Elsevier HS Journals, Inc. Published by Elsevier Inc. All rights reserved.
