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Population pharmaco...
Population pharmacokinetics and pharmacogenetics of ritonavir-boosted darunavir in the presence of raltegravir or tenofovir disoproxil fumarate/emtricitabine in HIV-infected adults and the relationship with virological response: a sub-study of the NEAT001/ANRS143 randomized trial
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- Dickinson, Laura (författare)
- University of Liverpool
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- Gurjar, Rohan (författare)
- University of Liverpool
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- Stöhr, Wolfgang (författare)
- University College London
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- Bonora, Stefano (författare)
- University of Turin
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- Owen, Andrew (författare)
- University of Liverpool
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- D’avolio, Antonio (författare)
- University of Turin
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- Cursley, Adam (författare)
- University College London
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- Molina, Jean-michel (författare)
- Paris Diderot University
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- Fäetkenheuer, Gerd (författare)
- University of Cologne
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- Vandekerckhove, Linos (författare)
- Ghent University Hospital,Ghent University
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- Di Perri, Giovanni (författare)
- University of Turin
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- Pozniak, Anton (författare)
- Chelsea and Westminster Hospital
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- Richert, Laura (författare)
- University of Bordeaux
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- Raffi, François (författare)
- Nantes University Hospital
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- Boffito, Marta (författare)
- Imperial College London
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- Odermarsky, Michal (creator_code:cre_t)
- Lund University,Lunds universitet,Barnkardiologi,Forskargrupper vid Lunds universitet,Children cardiology,Lund University Research Groups
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(creator_code:org_t)
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- 2019-11-21
- 2020
- Engelska.
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Ingår i: Journal of Antimicrobial Chemotherapy. - : Oxford University Press (OUP). - 0305-7453 .- 1460-2091. ; 75:3, s. 628-639
- Relaterad länk:
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https://academic.oup...
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http://dx.doi.org/10...
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https://discovery.uc...
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https://lup.lub.lu.s...
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https://doi.org/10.1...
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Abstract
Ämnesord
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- Objectives: NEAT001/ANRS143 demonstrated non-inferiority of once-daily darunavir/ritonavir (800/100 mg) + twice-daily raltegravir (400 mg) versus darunavir/ritonavir + tenofovir disoproxil fumarate/emtricitabine (245/200 mg once daily) in treatment-naive patients. We investigated the population pharmacokinetics of darunavir, ritonavir, tenofovir and emtricitabine and relationships with demographics, genetic polymorphisms and virological failure. Methods: Non-linear mixed-effects models (NONMEM v. 7.3) were applied to determine pharmacokinetic parameters and assess demographic covariates and relationships with SNPs (SLCO3A1, SLCO1B1, NR1I2, NR1I3, CYP3A5∗3, CYP3A4∗22, ABCC2, ABCC10, ABCG2 and SCL47A1). The relationship between model-predicted darunavir AUC0-24 and C24 with time to virological failure was evaluated by Cox regression. Results: Of 805 enrolled, 716, 720, 347 and 361 were included in the darunavir, ritonavir, tenofovir and emtricitabine models, respectively (11% female, 83% Caucasian). No significant effect of patient demographics or SNPs was observed for darunavir or tenofovir apparent oral clearance (CL/F); coadministration of raltegravir did not influence darunavir or ritonavir CL/F. Ritonavir CL/F decreased by 23% in NR1I2 63396C>T carriers and emtricitabine CL/F was linearly associated with creatinine clearance (P<0.001). No significant relationship was demonstrated between darunavir AUC0-24 or C24 and time to virological failure [HR (95% CI): 2.28 (0.53-9.80), P=0.269; and 1.82 (0.61-5.41), P=0.279, respectively]. Conclusions: Darunavir concentrations were unaltered in the presence of raltegravir and not associated with virological failure. Polymorphisms investigated had little impact on study-drug pharmacokinetics. Darunavir/ritonavir + raltegravir may be an appropriate option for patients experiencing NRTI-associated toxicity.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Infektionsmedicin (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Infectious Medicine (hsv//eng)
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Dickinson, Laura
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Gurjar, Rohan
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Stöhr, Wolfgang
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Bonora, Stefano
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Owen, Andrew
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D’avolio, Antoni ...
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visa fler...
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Cursley, Adam
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Molina, Jean-mic ...
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Fäetkenheuer, Ge ...
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Vandekerckhove, ...
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Di Perri, Giovan ...
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Pozniak, Anton
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Richert, Laura
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Raffi, François
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Boffito, Marta
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Odermarsky, Mich ...
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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Journal of Antim ...
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Lunds universitet