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Effects of boceprevir and telaprevir on the pharmacokinetics of dolutegravir

AIMS: The aim was to evaluate the effect of boceprevir and telaprevir on dolutegravir pharmacokinetics (PK); the effect of dolutegravir on boceprevir and telaprevir PK was assessed through comparison with historical data for each hepatitis C virus (HCV) drug's prescribing information alone. MET...

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Autores principales: Johnson, Mark, Borland, Julie, Chen, Shuguang, Savina, Paul, Wynne, Brian, Piscitelli, Stephen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BlackWell Publishing Ltd 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4243878/
https://www.ncbi.nlm.nih.gov/pubmed/24838177
http://dx.doi.org/10.1111/bcp.12428
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author Johnson, Mark
Borland, Julie
Chen, Shuguang
Savina, Paul
Wynne, Brian
Piscitelli, Stephen
author_facet Johnson, Mark
Borland, Julie
Chen, Shuguang
Savina, Paul
Wynne, Brian
Piscitelli, Stephen
author_sort Johnson, Mark
collection PubMed
description AIMS: The aim was to evaluate the effect of boceprevir and telaprevir on dolutegravir pharmacokinetics (PK); the effect of dolutegravir on boceprevir and telaprevir PK was assessed through comparison with historical data for each hepatitis C virus (HCV) drug's prescribing information alone. METHODS: This was a single-centre, randomized, open-label, two-cohort, two-period, one-way study in healthy adult subjects. Dolutegravir 50 mg once daily was administered for 5 days in Period 1, and dolutegravir 50 mg once daily was coadministered with either boceprevir 800 mg every 8 h (Cohort 1) or telaprevir 750 mg every 8 h (Cohort 2) for 10 days in Period 2. RESULTS: No deaths or serious adverse events were reported during the study. Four subjects were withdrawn from the study because of adverse events (elevated alanine aminotransferase, cellulitis, increased serum creatinine and dizziness). One subject became pregnant during the study. Coadministration of dolutegravir with boceprevir had no effect on dolutegravir area under the plasma concentration–time curve (AUC) and maximal plasma concentration (C(max)) and caused a small increase in concentration at the end of the dosing interval (C(τ); 8%). Coadministration of dolutegravir with telaprevir resulted in increased dolutegravir plasma exposures compared with those after administration of dolutegravir alone; AUC(0–)(τ), C(max) and C(τ) increased by 25, 19 and 37%, respectively. Coadministration of boceprevir or telaprevir with dolutegravir had no clinically significant effect on dolutegravir PK. Plasma boceprevir and telaprevir PK data for either combined treatment were similar to historical data, indicating no effect of dolutegravir on boceprevir or telaprevir exposure. CONCLUSIONS: Dolutegravir can be coadministered with boceprevir or telaprevir in patients coinfected with HIV and HCV with no dose adjustment.
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spelling pubmed-42438782014-12-31 Effects of boceprevir and telaprevir on the pharmacokinetics of dolutegravir Johnson, Mark Borland, Julie Chen, Shuguang Savina, Paul Wynne, Brian Piscitelli, Stephen Br J Clin Pharmacol Drug Interactions AIMS: The aim was to evaluate the effect of boceprevir and telaprevir on dolutegravir pharmacokinetics (PK); the effect of dolutegravir on boceprevir and telaprevir PK was assessed through comparison with historical data for each hepatitis C virus (HCV) drug's prescribing information alone. METHODS: This was a single-centre, randomized, open-label, two-cohort, two-period, one-way study in healthy adult subjects. Dolutegravir 50 mg once daily was administered for 5 days in Period 1, and dolutegravir 50 mg once daily was coadministered with either boceprevir 800 mg every 8 h (Cohort 1) or telaprevir 750 mg every 8 h (Cohort 2) for 10 days in Period 2. RESULTS: No deaths or serious adverse events were reported during the study. Four subjects were withdrawn from the study because of adverse events (elevated alanine aminotransferase, cellulitis, increased serum creatinine and dizziness). One subject became pregnant during the study. Coadministration of dolutegravir with boceprevir had no effect on dolutegravir area under the plasma concentration–time curve (AUC) and maximal plasma concentration (C(max)) and caused a small increase in concentration at the end of the dosing interval (C(τ); 8%). Coadministration of dolutegravir with telaprevir resulted in increased dolutegravir plasma exposures compared with those after administration of dolutegravir alone; AUC(0–)(τ), C(max) and C(τ) increased by 25, 19 and 37%, respectively. Coadministration of boceprevir or telaprevir with dolutegravir had no clinically significant effect on dolutegravir PK. Plasma boceprevir and telaprevir PK data for either combined treatment were similar to historical data, indicating no effect of dolutegravir on boceprevir or telaprevir exposure. CONCLUSIONS: Dolutegravir can be coadministered with boceprevir or telaprevir in patients coinfected with HIV and HCV with no dose adjustment. BlackWell Publishing Ltd 2014-11 2014-10-20 /pmc/articles/PMC4243878/ /pubmed/24838177 http://dx.doi.org/10.1111/bcp.12428 Text en © 2014 ViiV Healthcare/GSK. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of The British Pharmacological Society. http://creativecommons.org/licenses/by-nc-nd/3.0/ This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
spellingShingle Drug Interactions
Johnson, Mark
Borland, Julie
Chen, Shuguang
Savina, Paul
Wynne, Brian
Piscitelli, Stephen
Effects of boceprevir and telaprevir on the pharmacokinetics of dolutegravir
title Effects of boceprevir and telaprevir on the pharmacokinetics of dolutegravir
title_full Effects of boceprevir and telaprevir on the pharmacokinetics of dolutegravir
title_fullStr Effects of boceprevir and telaprevir on the pharmacokinetics of dolutegravir
title_full_unstemmed Effects of boceprevir and telaprevir on the pharmacokinetics of dolutegravir
title_short Effects of boceprevir and telaprevir on the pharmacokinetics of dolutegravir
title_sort effects of boceprevir and telaprevir on the pharmacokinetics of dolutegravir
topic Drug Interactions
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4243878/
https://www.ncbi.nlm.nih.gov/pubmed/24838177
http://dx.doi.org/10.1111/bcp.12428
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