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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 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.

SUBMITTER: Belkhir L

PROVIDER: S-EPMC5943329 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature

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

Belkhir Leïla L Seguin-Devaux Carole C Elens Laure L Pauly Caroline C Gengler Nicolas N Schneider Serge S Ruelle Jean J Haufroid Vincent V Vandercam Bernard B

Scientific reports 20180509 1

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 ...[more]

PMID: 29743555

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Dataset Information

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

Publications

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

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