Relationship between the CYP2D6 genotype and the steady-state plasma concentrations of trazodone and its active metabolite m-chlorophenylpiperazine
Relationship between the CYP2D6 genotype and the steady-state plasma concentrations of trazodone and its active metabolite m-chlorophenylpiperazine
复制标题
CYP2D6基因型与曲唑酮及其活性代谢物间氯苯基哌嗪稳态血浆浓度的关系
作者：
K. Mihara;K. Otani;A. Suzuki;N. Yasui;H. Nakano;Xianmin Meng;T. Ohkubo;T. Nagasaki;S. Kaneko;S. Tsuchida;K. Sugawara;F. Gonzalez
在54名睡前服用曲唑酮150 mg的日本抑郁症患者中，研究了细胞色素P450（P450）2D 6基因型与曲唑酮及其活性代谢物间氯苯基哌嗪（mCPP）稳态血药浓度（Css）之间的关系。通过使用等位基因特异性PCR分析，鉴定了野生型等位基因、导致酶活性缺失的3个突变等位基因（CYP 2D 6A、CYP 2D 6 B和CYP 2D 6D）和导致酶活性降低的1个突变等位基因（CYPZD 6 Ch）。在17例无突变等位基因、27例有1个突变等位基因和10例有2个突变等位基因的病例中，曲唑酮的Css（校正至中位体重）的平均值（范围）分别为556（281-1115）、643（302-1362）和671（234-1418）ng/ml，而mCPP值分别为60（35-121）、65（33-99）和58（38-112）ng/ml。 三组间曲唑酮（F = 0.80，P = 0.45）和mCPP（F = 0.49，P =0.61）的Css无显著性差异。 因此，本研究表明，CYP 2D 6基因型不能预测这些化合物的Css。
Abstract The relationship between the cytochrome P450 (CYP) 2D6 genotype and the steady-state plasma concentrations (Css) of trazodone and its active metabolite m-chlorophenylpiperazine (mCPP) was studied in 54 depressed Japanese patients receiving trazodone 150 mg at bedtime. By use of allele-specific PCR analysis, the wild type allele, three mutated alleles causing absent enzyme activity (CYP2D6A, CYP2D6B and CYP2D6D) and one mutated allele causing decreased enzyme activity (CYPZD6 Ch) were identified. The means (ranges) of the Css of trazodone, corrected to the median body weight in 17 cases with no mutated allele, 27 cases with one mutated allele and 10 cases with two mutated alleles, were 556 (281–1115), 643 (302–1362) and 671 (234–1418) ng/ml, respectively, while the values of mCPP were 60 (35–121), 65 (33–99) and 58 (38–112) ng/ml, respectively. Neither the Css of trazodone (F = 0.80, P = 0.45) nor that of mCPP (F = 0.49, P = 0.61) significantly differed among the three groups. The present study thus suggests that the CYP2D6 genotype cannot predict the Css of these compounds.
鉴定出外显子 3 中具有单碱基缺失的新变异 CYP2D6 等位基因及其与代谢不良表型的关联。
影响因子：
3.5
作者：
Saxena,R;Shaw,GL;Relling,MV;Frame,JN;Moir,DT;Evans,WE;Caporaso,N;Weiffenbach,B
通讯作者：
Weiffenbach,B