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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Nature Portfolio
2018-05-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-018-25803-z |
| _version_ | 1818431492261412864 |
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| 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 |
| collection | DOAJ |
| 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 UGT1A1*1/*1 while 50% (n = 48) and 6% (n = 6) were UGT1A1*28 and UGT1A1*36 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 UGT1A1*1/*1, UGT1A1*28 and UGT1A1*36 carriers, respectively. Only the difference between UGT1A1*1/*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 UGT1A1*1/*1, UGT1A1*28 and UGT1A1*36 carriers, respectively. Only the difference between UGT1A1*1/*1 and *28 carriers was statistically significant (p = 0.004) with an allele-dependent effect: UGT1A1*28 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 UGT1A1*28 polymorphism has a significant impact on RAL metabolism: UGT1A1*28 carriers being characterized by higher [RAL]plasma and lower MR. |
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| id | doaj.art-c11be330a5f74880b09545120987b42d |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-14T15:50:10Z |
| publishDate | 2018-05-01 |
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| spelling | doaj.art-c11be330a5f74880b09545120987b42d2022-12-21T22:55:24ZengNature PortfolioScientific Reports2045-23222018-05-01811810.1038/s41598-018-25803-zImpact of UGT1A1 polymorphisms on Raltegravir and its glucuronide plasma concentrations in a cohort of HIV-1 infected patientsLeïla Belkhir0Carole Seguin-Devaux1Laure Elens2Caroline Pauly3Nicolas Gengler4Serge Schneider5Jean Ruelle6Vincent Haufroid7Bernard Vandercam8AIDS Reference center, Cliniques Universitaires Saint-LucDepartment of Infection and Immunity, Luxembourg Institute of HealthLouvain centre for Toxicology and Applied Pharmacology (LTAP), Institut de recherche expérimentale et clinique (IREC), Université catholique de Louvain (UCL)Department of toxicology, Laboratoire National de SantéDepartment of toxicology, Laboratoire National de SantéDepartment of toxicology, Laboratoire National de SantéAIDS reference laboratory, IREC, UCLLouvain centre for Toxicology and Applied Pharmacology (LTAP), Institut de recherche expérimentale et clinique (IREC), Université catholique de Louvain (UCL)AIDS Reference center, Cliniques Universitaires Saint-LucAbstract 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 UGT1A1*1/*1 while 50% (n = 48) and 6% (n = 6) were UGT1A1*28 and UGT1A1*36 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 UGT1A1*1/*1, UGT1A1*28 and UGT1A1*36 carriers, respectively. Only the difference between UGT1A1*1/*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 UGT1A1*1/*1, UGT1A1*28 and UGT1A1*36 carriers, respectively. Only the difference between UGT1A1*1/*1 and *28 carriers was statistically significant (p = 0.004) with an allele-dependent effect: UGT1A1*28 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 UGT1A1*28 polymorphism has a significant impact on RAL metabolism: UGT1A1*28 carriers being characterized by higher [RAL]plasma and lower MR.https://doi.org/10.1038/s41598-018-25803-z |
| spellingShingle | 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 Scientific Reports |
| title | 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_short | 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 |
| url | https://doi.org/10.1038/s41598-018-25803-z |
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