Darunavir/cobicistat once daily for the treatment of HIV

Kakuda, Thomas N.; Crauwels, Herta; Opsomer, Magda; Tomaka, Frank; Casteele, Tom Van de; Vanveggel, Simon; Iterbeke, Koen; Smedt, Goedele De

doi:10.1586/14787210.2015.1033400

Cited by 13 publications

(9 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“… *The postpartum visit darunavir AUC 24 h and C 0 h were similar to those observed in a historical phase 3b study of HIV‐1‐infected adults treated with a darunavir/cobicistat‐based regimen (mean ± SD AUC 24 h : 102 000 ± 33 100 ng h/mL; C 0 h : 2150 ± 1320 ng/mL) . † For within‐subject comparisons, BLQ values were excluded for C min ; second trimester, n = 6; third trimester, n = 6; and postpartum, n = 5.…”

Section: Resultsmentioning

confidence: 79%

Reduced exposure to darunavir and cobicistat in HIV‐1‐infected pregnant women receiving a darunavir/cobicistat‐based regimen

et al. 2019

View full text Add to dashboard Cite

ObjectivesThe aim of the study was to evaluate darunavir and cobicistat pharmacokinetics in pregnant women with HIV-1 infection. MethodsThis phase 3b, open-label study enrolled HIV-1-infected pregnant women (18-26 weeks of gestation) receiving combination antiretroviral therapy with once-daily darunavir/cobicistat 800/ 150 mg. The plasma pharmacokinetics of darunavir (total and unbound) and cobicistat were assessed over 24 h during the second and third trimesters (24-28 and 34-38 weeks of gestation, respectively) and 6-12 weeks postpartum. Pharmacokinetic parameters [area under the plasma concentration-time curve over 24 h (AUC 24 h ), maximum plasma concentration (C max ) and minimum plasma concentration (C min )] were derived using noncompartmental analysis and compared using linear mixed effects modelling (pregnancy versus postpartum). Antiviral activity and safety were evaluated. ResultsSeven women were enrolled in the study; six completed it. Total darunavir exposure was lower during pregnancy than postpartum (AUC 24 h , 50-56% lower; C max , 37-49% lower; C min , 89-92% lower); unbound darunavir exposure was also reduced (AUC 24 h , 40-45% lower; C max , 32-41% lower; C min , 88-92% lower). Cobicistat exposure was also lower during pregnancy than postpartum (AUC 24 h , 49-63% lower; C max , 27-50% lower; C min , 83% lower). At study completion, five of six (83%) women were virologically suppressed (HIV-1 RNA < 50 copies/mL). There was one virological failure (the patient was nonadherent; no emerging genotypic resistance was observed and susceptibility to antiretrovirals was maintained). No mother-to-child transmission was detected among six infants born to the six women who completed the study. Overall, darunavir/cobicistat was well tolerated in women and infants. ConclusionsIn view of markedly reduced darunavir and cobicistat exposures during pregnancy, this combination is not recommended in HIV-1-infected pregnant women.

show abstract

Section: Resultsmentioning

confidence: 79%

Reduced exposure to darunavir and cobicistat in HIV‐1‐infected pregnant women receiving a darunavir/cobicistat‐based regimen

et al. 2019

View full text Add to dashboard Cite

show abstract

“…DRV is extensively metabolized by cytochrome P450 (CYP), mainly CYP3A . COBI is a potent mechanism‐based inhibitor of CYP3A and thus a pharmacoenhancer of DRV …”

mentioning

confidence: 99%

Bioequivalence of the Once‐Daily Single‐Tablet Regimen of Darunavir, Cobicistat, Emtricitabine, and Tenofovir Alafenamide Compared to Combined Intake of the Separate Agents and the Effect of Food on Bioavailability

Crauwels

Baugh

Landuyt

et al. 2018

Clinical Pharm in Drug Dev

Self Cite

View full text Add to dashboard Cite

The effect of food on the bioavailability of the components of the once‐daily, single‐tablet human immunodeficiency virus (HIV) type 1 regimen containing darunavir (DRV 800 mg), cobicistat (COBI 150 mg), emtricitabine (FTC 200 mg), and tenofovir alafenamide (TAF 10 mg) (D/C/F/TAF) (NCT02475135) and the bioequivalence of D/C/F/TAF versus combined intake of the separate agents (NCT02578550) were evaluated. These were 2 phase 1, open‐label, randomized, 2‐period crossover studies (7‐day washout between treatments) in HIV‐negative healthy volunteers. Twenty‐four participants each received a single dose of D/C/F/TAF in fasted conditions (test) or after a standardized high‐fat breakfast (reference). Ninety‐six participants each received a single dose of D/C/F/TAF (test) or combined intake of a single DRV 800‐mg tablet, a COBI 150‐mg tablet, and an FTC/TAF 200/10‐mg tablet (reference), both after a standardized regular‐calorie, regular‐fat breakfast. Pharmacokinetic profiles for all D/C/F/TAF components, safety, and tolerability were assessed. Following D/C/F/TAF in fasted conditions, DRV peak concentration, area under the concentration‐time curve from time of administration until the last time point with a measurable concentration (AUC)last, and extrapolated to infinity (AUCinf) were lower by 45%, 34%, and 30%, respectively, compared with fed conditions, with no clinically relevant differences in COBI, FTC, or TAF exposures between fed and fasted conditions. In the bioequivalence study 90% confidence intervals of the geometric mean ratios of all main pharmacokinetic parameters were within the 80.00% to 125.00% bioequivalence limits for DRV, COBI, FTC, and TAF. No grade 3/4 adverse events (AEs), serious AEs, deaths, or discontinuations due to AEs occurred. D/C/F/TAF is bioequivalent to combined administration of the separate agents. Consistent with other (co)formulations of DRV, DRV exposure was lower in fasted than in fed conditions as evaluated when taken with food, so D/C/F/TAF should be taken with food.

show abstract

“…In Phase I trials, cobicistat was shown to be a comparable therapeutic enhancer to ritonavir in combination with atazanavir, integrase inhibitor elvitegravir, or midazolam (a CYP3A test substrate) [52]. An atazanavir / cobicistat dependent regimen provided efficacy and protection comparable to an atazanavir / ritonavir regimen in phase II studies [50]. However, a randomized trial at the Shanghai Public Health Clinical Center (SPHCC) evaluating Cobicistat for COVID-19 has shown that it has not been successful and can be reassessed.…”

Section: Cobicistatmentioning

confidence: 99%

“…The Chinese authorities have indicated that Darunavir against 2019-nCoV may be successful. In vitro cell studies have shown that Darunavir can effectively inhibit replication of the new strain, at a concentration of 300 micromolar, according to preliminary research Darunavir, in conjunction with cobicistat, will be used in patients with COVID-19 pneumonia in trial number NCT04252274 (50). Such a mixture is currently approved by the United States Food and Drug Administration (FDA) in AIDS treatment.…”

Section: Darunavirmentioning

confidence: 99%

Potential Drug Candidates Underway Several Registered Clinical Trials for Battling COVID-19

Mina¹,

Rahman²,

Das³

et al. 2020

Preprint

View full text Add to dashboard Cite

The emergence of new type of viral pneumonia cases in China, on December 31, 2019; identified as the cause of human coronavirus, labeled as "COVID-19," took a heavy toll of death and reported cases of infected people all over the world, with the potential to spread widely and rapidly, achieved worldwide prominence but arose without the procurement guidance. There is an immediate need for active intervention and fast drug discovery against the 2019-nCoV outbreak. Herein, the study provides numerous candidates of drugs (either alone or integrated with another drugs) which could prove to be effective against 2019-nCoV, are under different stages of clinical trials. This review will offer rapid identification of a number of repurposable drugs and potential drug combinations targeting 2019-nCoV and preferentially allow the international research community to evaluate the findings, to validate the efficacy of the proposed drugs in prospective trials and to lead potential clinical practices.

show abstract

Darunavir/cobicistat once daily for the treatment of HIV

Cited by 13 publications

References 48 publications

Reduced exposure to darunavir and cobicistat in HIV‐1‐infected pregnant women receiving a darunavir/cobicistat‐based regimen

Reduced exposure to darunavir and cobicistat in HIV‐1‐infected pregnant women receiving a darunavir/cobicistat‐based regimen

Bioequivalence of the Once‐Daily Single‐Tablet Regimen of Darunavir, Cobicistat, Emtricitabine, and Tenofovir Alafenamide Compared to Combined Intake of the Separate Agents and the Effect of Food on Bioavailability

Potential Drug Candidates Underway Several Registered Clinical Trials for Battling COVID-19

Contact Info

Product

Resources

About