Factors Affecting Steady-state Plasma Concentrations of Enantiomeric Mirtazapine and its Desmethylated Metabolites in Japanese Psychiatric Patients.
Factors Affecting Steady-state Plasma Concentrations of Enantiomeric Mirtazapine and its Desmethylated Metabolites in Japanese Psychiatric Patients.
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影响日本精神病患者中对映体米氮平及其去甲基化代谢物稳态血浆浓度的因素。
DOI：
10.1055/s-0035-1565069
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发表时间：
2015
影响因子：
4.3
通讯作者：
Shimoda K.
中科院分区：
文献类型：
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作者：
Hayashi Y;Watanabe T;Aoki A;Ishiguro S;Ueda M;Akiyama K;Kato K;Inoue Y;Tsuchimine S;Yasui-Furukori N;Shimoda K.
引言：本研究评价了CYP 2D 6 * 10基因型对日本患者中对映体米氮平（MIR）和N-去甲基米氮平（DMIR）稳态血药浓度的影响。使用立体选择性液相色谱法测量MIR和DMIR对映体的稳态血浆浓度。结果：经剂量和体重校正后，吸烟组（n=15）的S-（+）-MIR显著低于非吸烟组（n=55）（15.1±17.8 vs. 23.9±17.8 ng/mL/mg/kg，Kruskal-Wallis检验，p=0.034）。单因素方差分析显示，CYP 2D 6 * 10纯合子组的S-（+）-MIR校正血浆浓度显著高于无变异等位基因组（p=0.034）。多元回归分析显示，CYP 2D 6 * 10等位基因数与S-（+）-MIR校正血药浓度呈显著正相关。结果表明：日本人S-（+）-MIR的校正血药浓度=15.9+7.30×（CYP 2D 6 * 10等位基因数）（R=0.279，p=0.023，决定系数（R2）=0.078）。
Introduction:This study evaluated the effects of theCYP2D6*10genotype on steady-state plasma concentrations of enantiomeric mirtazapine (MIR) and N-desmethylmirtazapine (DMIR) in Japanese patients.Methods:Subjects were 77 Japanese patients treated with racemic MIR. Steady-state plasma concentrations of MIR and DMIR enantiomers were measured using stereoselective liquid chromatography. Polymerase chain reaction was used to determine theCYP2D6genotypes.Results:After correcting for dose and body weight, smokers (n=15) had significantly lower S-(+)-MIR than nonsmokers (n=55) (15.1±17.8 vs. 23.9±17.8 ng/mL/mg/kg, Kruskal-Wallis test, p=0.034). One-way analysis of variance revealed thatCYP2D6*10homozygotes had significantly higher corrected plasma concentrations of S-(+)-MIR than the no-variant allele group (p=0.034). Multiple regression analysis revealed a significant positive correlation between the number ofCYP2D6*10alleles and corrected plasma concentrations of S-(+)-MIR. These results yielded the following final model: corrected plasma concentration of S-(+)-MIR=15.9+7.30×(number ofCYP2D6*10alleles) (R=0.279, p=0.023, coefficient of determination (R2)=0.078).Conclusion:HomozygousCYP2D6*10alleles and smoking have a significant impact on the metabolism of S-(+)-MIR in Japanese patients.