Pharmacokinetics of cobicistat boosted‐elvitegravir administered in combination with rosuvastatin

Custodio, Joseph M.; Wang, Hui; Jia, Hao; Lepist, Eve-Irene; Ray, Adrian S.; Andrews, Jessica L.; Ling, Kah Hiing John; Cheng, Andrew; Kearney, Brian P.; Ramanathan, S.

doi:10.1002/jcph.256

Cited by 33 publications

(24 citation statements)

References 22 publications

(46 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In a recent analysis of 10 healthy subjects co-administered COBI/EVG with rosuvastatin, there was an increase in the rosuvastatin C max of89%, but only a 38% increase in the AUC, with no changes in the T max or the T 1/2 of the drug. 54 There were no differences in the pharmacokinetics of COBI or EVG when administered with rosuvastatin. 54 Based on the findings of this study, the authors recommended that rosuvastatin could be co-administered with COBI/EVG.…”

Section: Drug-drug Interactions For the Treatment Of Chronic Co-morbimentioning

confidence: 87%

See 1 more Smart Citation

Drug Interactions and Antiretroviral Drug Monitoring

et al. 2014

View full text Add to dashboard Cite

Due to the improved longevity afforded by combination antiretroviral therapy (cART), HIV-infected individuals are developing several non-AIDS related comorbid conditions. Consequently, medical management of the HIV-infected population is increasingly complex, with a growing list of potential drug-drug interactions (DDIs). This article reviews some of the most relevant and emerging potential interactions between antiretroviral medications and other agents. The most common DDIs are those involving protease inhibitors or non-nucleoside reverse transcriptase inhibitors which alter the cytochrome P450 enzyme system and/or drug transporters such as p-glycoprotein. Of note are the new agents for the treatment of chronic hepatitis C virus infection. These new classes of drugs and others drugs which are increasingly used in this patient population represent a significant challenge with regard to achieving the goals of effective HIV suppression and minimization of drug-related toxicities. Awareness of DDIs and a multidisciplinary approach are imperative in reaching these goals.

show abstract

Section: Drug-drug Interactions For the Treatment Of Chronic Co-morbimentioning

confidence: 87%

“…54 There were no differences in the pharmacokinetics of COBI or EVG when administered with rosuvastatin. 54 Based on the findings of this study, the authors recommended that rosuvastatin could be co-administered with COBI/EVG.…”

Section: Drug-drug Interactions For the Treatment Of Chronic Co-morbimentioning

confidence: 87%

Drug Interactions and Antiretroviral Drug Monitoring

et al. 2014

View full text Add to dashboard Cite

show abstract

“…The combination of cobicistat with elvitegravir had only a modest effect on rosuvastatin exposure that was not clinically significant, allowing this combination to be used without dose adjustment [45] ": Increase; #: Decrease; AUC tau /AUC last /AUC inf : Area under the concentration-time curve to the end of the dosing period/to the last measurable concentration/to infinite time; C max : Maximum plasma concentration; C tau or C min : Plasma concentration at the end of the dosing period or minimum plasma concentration; FDC: Fixed-dose combination; HMG: 3-hydroxy-3-methyl-glutaryl; TDF: Tenofovir disoproxil fumarate.…”

Section: Darunavir/cobicistat Fdc Clinical Development Programmentioning

confidence: 97%

“…Cobicistat increased digoxin maximum plasma concentration (C max ) by 41% and exposure (area under the plasma concentrationtime curve [AUC]) by 20% [44]. The combination of cobicistat with elvitegravir had only a modest effect on rosuvastatin exposure that was not clinically significant, allowing this combination to be used without dose adjustment [45]. Similarly, drug-drug interaction studies of cobicistat and elvitegravir combined with opioids showed no clinically significant effect on methadone, buprenorphine/naloxone or cobicistat [46,47].…”

Section: Drug-drug Interactionsmentioning

confidence: 99%

Darunavir/cobicistat once daily for the treatment of HIV

Kakuda

Crauwels

Opsomer

et al. 2015

Expert Review of Anti-infective Therapy

View full text Add to dashboard Cite

A current focus in HIV management is improving adherence by minimizing pill burden with convenient formulations, including fixed-dose combinations (FDCs). Darunavir, a HIV protease inhibitor, co-administered with low-dose ritonavir (800/100 mg once daily), is recommended in guidelines in combination with other antiretrovirals for HIV patients with no darunavir resistance-associated mutations. Cobicistat is an alternative agent to ritonavir for boosting plasma drug levels of darunavir among other antiretrovirals. Cobicistat is a more specific cytochrome P450 3A inhibitor than ritonavir without enzyme-inducing properties. This review describes the differing effects of cobicistat and ritonavir on metabolic enzymes, which explains their differing drug-drug interactions, and summarizes some of the studied drug-drug interactions for cobicistat. It also outlines the clinical development and data for a once-daily darunavir/cobicistat FDC. This FDC thus allows for a once-daily treatment regimen (including background antiretrovirals) with reduced pill burden.

show abstract

“…It is possible that EVG has slower uptake kinetics in macrophages than MGBG. Cobicistat, a potent inhibitor of cytochrome P450 3A enzymes and intestinal transport proteins, has been used together with EVG to enhance overall drug absorption in the clinical settings (68,69).…”

Section: Figmentioning

confidence: 99%

Inhibition of HIV Expression and Integration in Macrophages by Methylglyoxal-Bis-Guanylhydrazone

Jin

McGrath

2015

J Virol

View full text Add to dashboard Cite

Macrophages are a target for infection with HIV and represent one of the viral reservoirs that are relatively resistant to current antiretroviral drugs. Here we demonstrate that methylglyoxal-bis-guanylhydrazone (MGBG), a polyamine analog and potent S-adenosylmethionine decarboxylase inhibitor, decreases HIV expression in monocytes and macrophages. MGBG is selectively concentrated by these cells through a mechanism consistent with active transport by the polyamine transporter. Using a macrophage-tropic reporter virus tagged with the enhanced green fluorescent protein, we demonstrate that MGBG decreases the frequency of HIV-infected cells. The effect is dose dependent and correlates with the production of HIV p24 in culture supernatants. This anti-HIV effect was further confirmed using three macrophage-tropic primary HIV isolates. Viral life cycle mapping studies show that MGBG inhibits HIV DNA integration into the cellular DNA in both monocytes and macrophages. O ne of the major remaining obstacles in treating human immunodeficiency type 1 (HIV-1)-related diseases is the elimination of viral reservoirs that contribute to persistent infection and chronic immune activation. Although highly active antiretroviral therapy (HAART) is effective at reducing the plasma viral load and slowing down the decline of CD4 ϩ T lymphocytes and dendritic cells, it has failed to eradicate the residual long-lived HIV-infected cellular reservoirs (1-3). At the molecular level, HAART successfully suppresses HIV RNA replication and decreases total viral DNA load in treated individuals. However, it fails to eliminate the integrated proviral DNA (4, 5). Even in HAART-treated patients with an undetectable plasma viral load, discontinuation of treatment is routinely associated with the reappearance of HIV RNA in circulation, confirming the presence of significant HIV proviral reservoirs in HAART-treated individuals (6, 7).HIV-1 cellular reservoirs include resting CD4 ϩ T lymphocytes and cells of the monocyte and macrophage lineage (1, 8, 9). Research on the HIV reservoirs has largely focused on T cells and more specifically a rare subset of resting memory CD4 T cells that has been reproducibly identified in the blood of patients with low or no detectible plasma viral loads (10). Cells of the monocyte and macrophage lineage may represent another mechanism for viral persistence. These cells are among the cells infected early upon exposure to HIV (11), and the presence of CCR5-utilizing "macrophage-tropic" forms of HIV in the plasma of essentially all newly infected individuals is consistent with the notion that macrophages represent an early target for HIV infection (12)(13)(14)(15). In contrast to CD4 T cells which die with effective HIV replication, macrophages are resistant to the cytopathic effect of the virus. Furthermore, macrophages and dendritic cells are capable of transmitting HIV to T cells or other macrophages via cell-cell contact (16). Depending on the origins of the virus, both cis-infection and trans-infection modes h...

show abstract

Pharmacokinetics of cobicistat boosted‐elvitegravir administered in combination with rosuvastatin

Cited by 33 publications

References 22 publications

Drug Interactions and Antiretroviral Drug Monitoring

Drug Interactions and Antiretroviral Drug Monitoring

Darunavir/cobicistat once daily for the treatment of HIV

Inhibition of HIV Expression and Integration in Macrophages by Methylglyoxal-Bis-Guanylhydrazone

Contact Info

Product

Resources

About