Tsuchimine Shoko, Ochi Shinichiro, Tajiri Misuzu, Suzuki Yutaro, Sugawara Norio, Inoue Yoshimasa, Yasui-Furukori Norio
Department of Neuropsychiatry, Hirosaki University Graduate School of Medicine, Hirosaki.
Department of Mental Disorder Research, National Institute of Neuroscience, Kodaira, Tokyo.
Ther Drug Monit. 2018 Jun;40(3):356-361. doi: 10.1097/FTD.0000000000000506.
Plasma concentrations of the S-enantiomer of citalopram were different between extensive and poor CYP2C19 metabolizers in healthy subjects and depressed patients. However, most studies applied dose-corrected concentrations. Thus, we studied the effects of polymorphisms of the CYP2C19 gene on raw plasma drug concentrations in Japanese patients with depression.
Subjects in this study consisted of 412 depressed patients receiving 5, 10, 15, or 20 mg of escitalopram once a day. Plasma concentrations of escitalopram and desmethylescitalopram were quantified using HPLC. CYP2C19 genotypes were identified using polymerase chain reaction methods.
There were no differences in the steady-state plasma concentrations of escitalopram or desmethylescitalopram in each dose group (5, 10, 15, or 20 mg of escitalopram) among CYP2C19 genotype groups. However, 1-way analysis of variance showed significant effects of CYP2C19 genotypes on the dose-adjusted plasma concentration of escitalopram but not in the dose-adjusted plasma concentration of desmethylescitalopram. Analysis of covariance including age, sex, and body weight showed significant effects of CYP2C19 genotypes on the dose-adjusted plasma concentration of escitalopram and the ratio of desmethylescitalopram to escitalopram.
These findings suggest that the CYP2C19 variants are associated with steady-state plasma concentrations of escitalopram to some extent but are not associated with desmethylescitalopram.
在健康受试者和抑郁症患者中，西酞普兰S-对映体的血浆浓度在CYP2C19代谢快和代谢慢的人群之间存在差异。然而，大多数研究采用的是剂量校正浓度。因此，我们研究了CYP2C19基因多态性对日本抑郁症患者血浆药物原始浓度的影响。
本研究的受试者包括412例每天服用5、10、15或20mg艾司西酞普兰的抑郁症患者。采用高效液相色谱法对艾司西酞普兰和去甲艾司西酞普兰的血浆浓度进行定量分析。采用聚合酶链反应方法鉴定CYP2C19基因型。
在各剂量组（5、10、15或20mg艾司西酞普兰）中，CYP2C19基因型组之间艾司西酞普兰或去甲艾司西酞普兰的稳态血浆浓度无差异。然而，单因素方差分析显示，CYP2C19基因型对艾司西酞普兰的剂量校正血浆浓度有显著影响，但对去甲艾司西酞普兰的剂量校正血浆浓度无显著影响。包括年龄、性别和体重的协方差分析显示，CYP2C19基因型对艾司西酞普兰的剂量校正血浆浓度以及去甲艾司西酞普兰与艾司西酞普兰的比值有显著影响。
这些发现表明，CYP2C19变体在一定程度上与艾司西酞普兰的稳态血浆浓度相关，但与去甲艾司西酞普兰无关。
