Impact of UGT1A1 polymorphisms on Raltegravir and its glucuronide plasma concentrations in a cohort of HIV-1 infected patients

Abstract The aim of this study was to evaluate the effect of UGT1A1 polymorphisms on Raltegravir (RAL) and its metabolite RAL-glucuronide trough plasma concentrations ([RAL]plasma and [RAL-glu]plasma) and on the metabolic ratio (MR): [RAL-glu]plasma/[RAL]plasma. UGT1A1 genotyping was performed on 96...

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Autores principales:	Leïla Belkhir, Carole Seguin-Devaux, Laure Elens, Caroline Pauly, Nicolas Gengler, Serge Schneider, Jean Ruelle, Vincent Haufroid, Bernard Vandercam
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/c11be330a5f74880b09545120987b42d
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spelling	oai:doaj.org-article:c11be330a5f74880b09545120987b42d2021-12-02T11:40:35ZImpact of UGT1A1 polymorphisms on Raltegravir and its glucuronide plasma concentrations in a cohort of HIV-1 infected patients10.1038/s41598-018-25803-z2045-2322https://doaj.org/article/c11be330a5f74880b09545120987b42d2018-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-25803-zhttps://doaj.org/toc/2045-2322Abstract The aim of this study was to evaluate the effect of UGT1A1 polymorphisms on Raltegravir (RAL) and its metabolite RAL-glucuronide trough plasma concentrations ([RAL]plasma and [RAL-glu]plasma) and on the metabolic ratio (MR): [RAL-glu]plasma/[RAL]plasma. UGT1A1 genotyping was performed on 96 patients. 44% (n = 42) were homozygous UGT1A11/1 while 50% (n = 48) and 6% (n = 6) were UGT1A128 and UGT1A136 carriers, respectively. The median concentration and interquartile range (IQR) of [RAL]plasma were 88.5 ng/ml (41.0–236), 168 ng/ml (85.8–318) and 92.5 ng/ml (36.4–316) for UGT1A11/1, UGT1A128 and UGT1A136 carriers, respectively. Only the difference between UGT1A11/1 and 28 carriers was statistically significant (p = 0.022). The median MR (IQR) were 5.8 (3–10), 2.9 (1.6–5.3) and 3.2 (1.7–5.9) for UGT1A11/1, UGT1A128 and UGT1A136 carriers, respectively. Only the difference between UGT1A11/1 and 28 carriers was statistically significant (p = 0.004) with an allele-dependent effect: UGT1A128 homozygous having lower MR than heterozygous carriers who show lower MR compared to 1/1. Except for the sensation of fatigue, this PK effect did not correlate with clinical adverse events or biological abnormalities. In Conclusion, we demonstrate that UGT1A128 polymorphism has a significant impact on RAL metabolism: UGT1A1*28 carriers being characterized by higher [RAL]plasma and lower MR.Leïla BelkhirCarole Seguin-DevauxLaure ElensCaroline PaulyNicolas GenglerSerge SchneiderJean RuelleVincent HaufroidBernard VandercamNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-8 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Leïla Belkhir Carole Seguin-Devaux Laure Elens Caroline Pauly Nicolas Gengler Serge Schneider Jean Ruelle Vincent Haufroid Bernard Vandercam Impact of UGT1A1 polymorphisms on Raltegravir and its glucuronide plasma concentrations in a cohort of HIV-1 infected patients
description	Abstract The aim of this study was to evaluate the effect of UGT1A1 polymorphisms on Raltegravir (RAL) and its metabolite RAL-glucuronide trough plasma concentrations ([RAL]plasma and [RAL-glu]plasma) and on the metabolic ratio (MR): [RAL-glu]plasma/[RAL]plasma. UGT1A1 genotyping was performed on 96 patients. 44% (n = 42) were homozygous UGT1A11/1 while 50% (n = 48) and 6% (n = 6) were UGT1A128 and UGT1A136 carriers, respectively. The median concentration and interquartile range (IQR) of [RAL]plasma were 88.5 ng/ml (41.0–236), 168 ng/ml (85.8–318) and 92.5 ng/ml (36.4–316) for UGT1A11/1, UGT1A128 and UGT1A136 carriers, respectively. Only the difference between UGT1A11/1 and 28 carriers was statistically significant (p = 0.022). The median MR (IQR) were 5.8 (3–10), 2.9 (1.6–5.3) and 3.2 (1.7–5.9) for UGT1A11/1, UGT1A128 and UGT1A136 carriers, respectively. Only the difference between UGT1A11/1 and 28 carriers was statistically significant (p = 0.004) with an allele-dependent effect: UGT1A128 homozygous having lower MR than heterozygous carriers who show lower MR compared to 1/1. Except for the sensation of fatigue, this PK effect did not correlate with clinical adverse events or biological abnormalities. In Conclusion, we demonstrate that UGT1A128 polymorphism has a significant impact on RAL metabolism: UGT1A1*28 carriers being characterized by higher [RAL]plasma and lower MR.
format	article
author	Leïla Belkhir Carole Seguin-Devaux Laure Elens Caroline Pauly Nicolas Gengler Serge Schneider Jean Ruelle Vincent Haufroid Bernard Vandercam
author_facet	Leïla Belkhir Carole Seguin-Devaux Laure Elens Caroline Pauly Nicolas Gengler Serge Schneider Jean Ruelle Vincent Haufroid Bernard Vandercam
author_sort	Leïla Belkhir
title	Impact of UGT1A1 polymorphisms on Raltegravir and its glucuronide plasma concentrations in a cohort of HIV-1 infected patients
title_short	Impact of UGT1A1 polymorphisms on Raltegravir and its glucuronide plasma concentrations in a cohort of HIV-1 infected patients
title_full	Impact of UGT1A1 polymorphisms on Raltegravir and its glucuronide plasma concentrations in a cohort of HIV-1 infected patients
title_fullStr	Impact of UGT1A1 polymorphisms on Raltegravir and its glucuronide plasma concentrations in a cohort of HIV-1 infected patients
title_full_unstemmed	Impact of UGT1A1 polymorphisms on Raltegravir and its glucuronide plasma concentrations in a cohort of HIV-1 infected patients
title_sort	impact of ugt1a1 polymorphisms on raltegravir and its glucuronide plasma concentrations in a cohort of hiv-1 infected patients
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/c11be330a5f74880b09545120987b42d
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Impact of UGT1A1 polymorphisms on Raltegravir and its glucuronide plasma concentrations in a cohort of HIV-1 infected patients

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