CYP2D6*10 polymorphism and the enantioselective O‐desmethylation of S‐(+)‐ and R‐(‐)‐venlafaxine in Japanese psychiatric patients
CYP2D6*10 polymorphism and the enantioselective O‐desmethylation of S‐(+)‐ and R‐(‐)‐venlafaxine in Japanese psychiatric patients
复制标题
日本精神病患者中 CYP2D6*10 多态性和 S-(+)- 和 R-(-)-文拉法辛的对映选择性 O-去甲基化
DOI：
10.1111/bcpt.13560
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发表时间：
2021
影响因子：
3.1
通讯作者：
Shimoda Kazutaka
中科院分区：
文献类型：
--
作者：
Sasaki Taro;Yasui‐Furukori Norio;Komahashi‐Sasaki Hazuki;Shinozaki Masataka;Hayashi Yuki;Kato Kazuko;Inoue Yoshimasa;Tsuchimine Shoko;Watanabe Takashi;Sugawara Norio;Shimoda Kazutaka
根据先前的研究，R‐（‐）‐文拉法辛（VEN）比S‐（+）‐VEN具有更高的对映体选择性，并且R‐（‐）‐VEN的血浆浓度取决于CYP2D6活性。因此，我们研究了cyp2d6 *10基因型对VEN对映体稳态浓度的药代动力学影响。研究对象为71名接受外消旋VEN治疗的日本抑郁症患者。测定VEN和O -去甲基文拉法辛（ODV）对映体的浓度。采用聚合酶链反应（PCR）检测cyp2d6 * 10基因型。S‐（+）‐VEN的血浆浓度约为R‐（‐）‐VEN的1.9倍。cyp2d6 *10两种突变等位基因的个体血浆S‐（+）‐VEN和R‐（‐）‐VEN的浓度似乎更高，尽管在cyp2d6 *10基因型之间血浆S‐（+）‐VEN和R‐（‐）‐VEN的水平没有显著差异。多元回归分析显示，cyp2d6 *10突变等位基因数量与R‐（‐）‐ODV/R‐（‐）‐VEN比值相关（P= 0.004）。这表明cyp2d6 *10突变影响R‐（‐）‐VEN和S‐（+）‐VEN的代谢。需要进一步的研究来检验这些发现如何影响临床实践。
According to previous studies, R‐(‐)‐venlafaxine (VEN) has higher enantioselectivity than S‐(+)‐VEN, and the plasma concentration of R‐(‐)‐VEN varies depending on CYP2D6 activity. Therefore, we examined the pharmacokinetic effects ofCYP2D6*10genotypes on the steady‐state concentrations of the enantiomers of VEN. The individuals were 71 Japanese depressed patients treated with racemic VEN. The concentrations of the enantiomers of VEN and O‐desmethylvenlafaxine (ODV) were measured. Polymerase chain reaction (PCR) was used to determine theCYP2D6*10genotypes. The plasma concentrations of S‐(+)‐VEN were approximately 1.9‐fold higher than those of R‐(‐)‐VEN. The plasma concentrations of S‐(+)‐VEN and R‐(‐)‐VEN seemed to be higher in individuals with two mutant alleles ofCYP2D6*10, although no significant differences were found in the plasma levels of S‐(+)‐VEN and R‐(‐)‐VEN betweenCYP2D6*10genotypes. The number of mutant alleles ofCYP2D6*10was a significant factor associated with the R‐(‐)‐ODV/R‐(‐)‐VEN ratio (P= .004) in multiple regression analysis. This suggests thatCYP2D6*10mutations affect the metabolism of R‐(‐)‐VEN and S‐(+)‐VEN. Further studies are needed to examine how these findings affect clinical practice.