Genetic Variants of Pregnane X Receptor (PXR) and CYP2B6 Affect the Induction of Bupropion Hydroxylation by Sodium Ferulate.
This study investigated the effects of pregnane X receptor (PXR/NR1I2) and CYP2B6 genetic variants on sodium ferulate (SF)-mediated induction of bupropion hydroxylation. The pharmacokinetics of bupropion and hydroxybupropion were evaluated after an oral dose of bupropion (150 mg) administered with a...
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2013-01-01
|
| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3686783?pdf=render |
| _version_ | 1818136643029172224 |
|---|---|
| author | Lichen Gao Yijing He Jie Tang Jiye Yin Zhengyu Huang Fangqun Liu Dongsheng Ouyang Xiaoping Chen Wei Zhang Zhaoqian Liu Honghao Zhou |
| author_facet | Lichen Gao Yijing He Jie Tang Jiye Yin Zhengyu Huang Fangqun Liu Dongsheng Ouyang Xiaoping Chen Wei Zhang Zhaoqian Liu Honghao Zhou |
| author_sort | Lichen Gao |
| collection | DOAJ |
| description | This study investigated the effects of pregnane X receptor (PXR/NR1I2) and CYP2B6 genetic variants on sodium ferulate (SF)-mediated induction of bupropion hydroxylation. The pharmacokinetics of bupropion and hydroxybupropion were evaluated after an oral dose of bupropion (150 mg) administered with and without SF pretreatment for 14 days in 33 healthy subjects. The area under the time-concentration curve (AUC) ratio of AUC_hyd (AUC(0-∞) of hydroxybupropion)/AUC_bup (AUC(0-∞) of bupropion) represents the CYP2B6 hydroxylation activity, which was significantly lower in CYP2B6*6 carriers (NR1I2 TGT noncarriers or carriers) than in noncarriers in both the basal and SF-induced states (p-value<0.05). AUC ratio and AUC_hyd of NR1I2 -24113AA variant were markedly lower than GA and GG genotypes (7.5±2.1 versus 14.5±3.3 and 20.6±1.1, and 8873±1431 versus 14,504±2218 and 17,586±1046) in the induced states. However, -24020(-)/(-) variant didn't show significant difference in the induction of CYP2B6 hydroxylation activity by SF compared with other -24020[GAGAAG]/(-) genotypes. NR1I2 TGT haplotype (-25385T+g.7635G+g.8055T) carriers exhibited a significantly decreased AUC ratio, compared with TGT noncarriers, in the basal states (7.6±1.0 versus 9.7±1.0), while this result wasn't observed in CYP2B6*6 noncarriers. Moreover, individuals with complete mutation-type [CYP2B6*6/*6+NR1I2 TGT+ -24113AA+ -24020 (-)/(-)] showed even lower percent difference of AUC ratio (8.7±1.2 versus 39.5±8.2) than those with complete wild-type. In conclusion, it is suggested that NR1I2 variants decrease the bupropion hydroxylation induced by SF treatment, particularly in CYP2B6*6 carriers.ChiCTR.org ChiCTR-TRC-11001285. |
| first_indexed | 2024-12-11T09:43:40Z |
| format | Article |
| id | doaj.art-bf94901fc2e64494a2b8d4984d6d5d2b |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-11T09:43:40Z |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-bf94901fc2e64494a2b8d4984d6d5d2b2022-12-22T01:12:37ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0186e6248910.1371/journal.pone.0062489Genetic Variants of Pregnane X Receptor (PXR) and CYP2B6 Affect the Induction of Bupropion Hydroxylation by Sodium Ferulate.Lichen GaoYijing HeJie TangJiye YinZhengyu HuangFangqun LiuDongsheng OuyangXiaoping ChenWei ZhangZhaoqian LiuHonghao ZhouThis study investigated the effects of pregnane X receptor (PXR/NR1I2) and CYP2B6 genetic variants on sodium ferulate (SF)-mediated induction of bupropion hydroxylation. The pharmacokinetics of bupropion and hydroxybupropion were evaluated after an oral dose of bupropion (150 mg) administered with and without SF pretreatment for 14 days in 33 healthy subjects. The area under the time-concentration curve (AUC) ratio of AUC_hyd (AUC(0-∞) of hydroxybupropion)/AUC_bup (AUC(0-∞) of bupropion) represents the CYP2B6 hydroxylation activity, which was significantly lower in CYP2B6*6 carriers (NR1I2 TGT noncarriers or carriers) than in noncarriers in both the basal and SF-induced states (p-value<0.05). AUC ratio and AUC_hyd of NR1I2 -24113AA variant were markedly lower than GA and GG genotypes (7.5±2.1 versus 14.5±3.3 and 20.6±1.1, and 8873±1431 versus 14,504±2218 and 17,586±1046) in the induced states. However, -24020(-)/(-) variant didn't show significant difference in the induction of CYP2B6 hydroxylation activity by SF compared with other -24020[GAGAAG]/(-) genotypes. NR1I2 TGT haplotype (-25385T+g.7635G+g.8055T) carriers exhibited a significantly decreased AUC ratio, compared with TGT noncarriers, in the basal states (7.6±1.0 versus 9.7±1.0), while this result wasn't observed in CYP2B6*6 noncarriers. Moreover, individuals with complete mutation-type [CYP2B6*6/*6+NR1I2 TGT+ -24113AA+ -24020 (-)/(-)] showed even lower percent difference of AUC ratio (8.7±1.2 versus 39.5±8.2) than those with complete wild-type. In conclusion, it is suggested that NR1I2 variants decrease the bupropion hydroxylation induced by SF treatment, particularly in CYP2B6*6 carriers.ChiCTR.org ChiCTR-TRC-11001285.http://europepmc.org/articles/PMC3686783?pdf=render |
| spellingShingle | Lichen Gao Yijing He Jie Tang Jiye Yin Zhengyu Huang Fangqun Liu Dongsheng Ouyang Xiaoping Chen Wei Zhang Zhaoqian Liu Honghao Zhou Genetic Variants of Pregnane X Receptor (PXR) and CYP2B6 Affect the Induction of Bupropion Hydroxylation by Sodium Ferulate. PLoS ONE |
| title | Genetic Variants of Pregnane X Receptor (PXR) and CYP2B6 Affect the Induction of Bupropion Hydroxylation by Sodium Ferulate. |
| title_full | Genetic Variants of Pregnane X Receptor (PXR) and CYP2B6 Affect the Induction of Bupropion Hydroxylation by Sodium Ferulate. |
| title_fullStr | Genetic Variants of Pregnane X Receptor (PXR) and CYP2B6 Affect the Induction of Bupropion Hydroxylation by Sodium Ferulate. |
| title_full_unstemmed | Genetic Variants of Pregnane X Receptor (PXR) and CYP2B6 Affect the Induction of Bupropion Hydroxylation by Sodium Ferulate. |
| title_short | Genetic Variants of Pregnane X Receptor (PXR) and CYP2B6 Affect the Induction of Bupropion Hydroxylation by Sodium Ferulate. |
| title_sort | genetic variants of pregnane x receptor pxr and cyp2b6 affect the induction of bupropion hydroxylation by sodium ferulate |
| url | http://europepmc.org/articles/PMC3686783?pdf=render |
| work_keys_str_mv | AT lichengao geneticvariantsofpregnanexreceptorpxrandcyp2b6affecttheinductionofbupropionhydroxylationbysodiumferulate AT yijinghe geneticvariantsofpregnanexreceptorpxrandcyp2b6affecttheinductionofbupropionhydroxylationbysodiumferulate AT jietang geneticvariantsofpregnanexreceptorpxrandcyp2b6affecttheinductionofbupropionhydroxylationbysodiumferulate AT jiyeyin geneticvariantsofpregnanexreceptorpxrandcyp2b6affecttheinductionofbupropionhydroxylationbysodiumferulate AT zhengyuhuang geneticvariantsofpregnanexreceptorpxrandcyp2b6affecttheinductionofbupropionhydroxylationbysodiumferulate AT fangqunliu geneticvariantsofpregnanexreceptorpxrandcyp2b6affecttheinductionofbupropionhydroxylationbysodiumferulate AT dongshengouyang geneticvariantsofpregnanexreceptorpxrandcyp2b6affecttheinductionofbupropionhydroxylationbysodiumferulate AT xiaopingchen geneticvariantsofpregnanexreceptorpxrandcyp2b6affecttheinductionofbupropionhydroxylationbysodiumferulate AT weizhang geneticvariantsofpregnanexreceptorpxrandcyp2b6affecttheinductionofbupropionhydroxylationbysodiumferulate AT zhaoqianliu geneticvariantsofpregnanexreceptorpxrandcyp2b6affecttheinductionofbupropionhydroxylationbysodiumferulate AT honghaozhou geneticvariantsofpregnanexreceptorpxrandcyp2b6affecttheinductionofbupropionhydroxylationbysodiumferulate |