Influence of CYP2C19 Polymorphism and Concomitant Antiepileptic Drugs on Serum Clobazam and N-Desmethyl Clobazam Concentrations in Patients With Epilepsy
Influence of CYP2C19 Polymorphism and Concomitant Antiepileptic Drugs on Serum Clobazam and N-Desmethyl Clobazam Concentrations in Patients With Epilepsy
复制标题
CYP2C19 多态性和合并抗癫痫药物对癫痫患者血清氯巴占和 N-去甲基氯巴占浓度的影响
DOI：
10.1097/ftd.0b013e318283b49a
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发表时间：
2013
影响因子：
2.5
通讯作者：
Y. Kagawa
中科院分区：
文献类型：
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作者：
Yoshiaki Yamamoto;Yukitoshi Takahashi;K. Imai;K. Miyakawa;S. Nishimura;R. Kasai;H. Ikeda;R. Takayama;Y. Mogami;Tokito Yamaguchi;K. Terada;K. Matsuda;Y. Inoue;Y. Kagawa
目的：探讨影响氯巴赞(CLB)及其活性代谢物[N-去甲基氯巴赞(NCLB)]代谢的因素，并评价其作为癫痫患者细胞色素P4502C19基因多态性指标的价值。方法：对来自238名日本患者的302份血清样本进行评估。计算血清CLB和NCLB浓度与CLB剂量的比值(CD比值)，并与CYP2C19表型进行比较。结果：NCLB在广泛代谢物(EM：*1/*1)、中间代谢物(IM：*1/*2或*1/*3)和较差代谢物(PM：*2/*2、*3/*3或*2/*3)中的平均Cd比值分别为3.1、4.9和21.6(mg/kg)。EM组和IM组同时使用肝酶诱导剂(苯妥英钠和卡马西平)可降低CLB的CD比率，增加NCLB的CD比率。在PM组，这些诱导剂也降低了CLB的CD比率，但不升高NCLB的CD比率。通过多元回归分析，体重与NCLB患者CD比率的增加呈正相关。同时使用唑尼沙胺和己三醇组也提高了EM组和IM组NCLB的CD比率，但PM组的CD比率几乎没有变化。以NCLB的CD比值为10.0(-mgr；g/m L)/(mg/kg)作为预测CYP2C19 PM状态的临界值，其敏感性和特异性分别为94.4%和95.7%。结论：NCLB与其他抗癫痫药物的相互作用表现出明显的表型差异。血清NCLB浓度的测定在临床上有助于PM表型的鉴定。
Objective: The aims of this study were to identify the factors influencing the metabolism of clobazam (CLB) and its active metabolite [N-desmethyl clobazam (NCLB)] and to evaluate the NCLB concentration as an indicator for CYP2C19 polymorphism in epileptic patients. Methods: A total of 302 serum samples from 238 Japanese patients were evaluated. The ratios of the serum CLB and NCLB concentrations to the CLB dose (CD ratios) were calculated and compared with CYP2C19 phenotypes. Results: The mean CD ratio of NCLB in extensive metabolizers (EM: *1/*1), intermediate metabolizers (IM: *1/*2 or *1/*3), and poor metabolizers (PM: *2/*2, *3/*3, or *2/*3) was 3.1, 4.9, and 21.6 (&mgr;g/mL)/(mg/kg), respectively. In the EM and IM groups, the concomitant use of hepatic enzyme inducers (phenytoin and carbamazepine) reduced the CD ratio of CLB and increased that of NCLB. In the PM group, these inducers also decreased the CD ratio for CLB but did not elevate the CD ratio for NCLB. Using multiple regression analysis, body weight showed a positive correlation with an increased CD ratio for NCLB. The concomitant use of zonisamide and stiripentol also elevated the CD ratio for NCLB in the EM and IM groups, but that of the PM group was almost unchanged. When the cut-off value of the CD ratio for NCLB was set as 10.0 (&mgr;g/mL)/(mg/kg) for predicting the CYP2C19 PM status, the sensitivity and specificity were 94.4% and 95.7%, respectively. Conclusions: The interaction between NCLB and other antiepileptic drugs showed marked differences among CYP2C19 phenotypes. Measurement of the serum NCLB concentration is clinically useful for identifying the PM phenotype.
关于细胞色素 P450 2C19 和 3A5 多态性对唑尼沙胺清除率影响的群体估计
影响因子：
2.5
作者：
Yusuke Okada;Takayuki Seo;T. Ishitsu;Atsuko Wanibuchi;Nami Hashimoto;Yoko Higa;K. Nakagawa
通讯作者：
K. Nakagawa
氯巴占 (CLB) 的低剂量附加疗法的功效是由其主要代谢物 N-去甲基-CLB 产生的
DOI：
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发表时间：
2007
期刊：
J Neurol Sci 263
影响因子：
--
作者：
Kinoshita M;Ikeda A;Begum T;Terada K;Shibasaki H
通讯作者：
Shibasaki H