Yamamoto Yoshiaki, Takahashi Yukitoshi, Imai Katsumi, Mogami Yukiko, Matsuda Kazumi, Nakai Masahiko, Kagawa Yoshiyuki, Inoue Yushi
Department of Clinical Research, National Epilepsy Center, Shizuoka Institute of Epilepsy and Neurological Disorders, 886 Urushiyama, Shizuoka 420-8688, Japan; Department of Clinical Pharmaceutics, Graduate School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Shizuoka 422-8526, Japan.
Department of Clinical Research, National Epilepsy Center, Shizuoka Institute of Epilepsy and Neurological Disorders, 886 Urushiyama, Shizuoka 420-8688, Japan.
Epilepsy Behav. 2014 May;34:124-6. doi: 10.1016/j.yebeh.2014.03.018. Epub 2014 Apr 17.
The aim of this study was to investigate the effect of sulthiame (STM) on the pharmacokinetics of clobazam (CLB) by determining the concentration to dose (CD) ratio (serum level (ng/ml) divided by dose (mg/kg)) of CLB and that of N-desmethyl-clobazam (DMCLB). We evaluated five patients (an adult and four children) whose serum CLB and DMCLB concentrations were monitored after the addition or discontinuation of STM. Four of the five patients were CYP2C19 intermediate metabolizers, and one patient was an extensive metabolizer. When the patients were taking STM (100-275 mg/day), the mean CD ratio of DMCLB increased by 82.6 to 248.5%, which was higher than when they were not using STM. The increase was dose-dependent. In contrast, the CD ratio of CLB remained stable after addition or discontinuation of STM. These data suggest that STM has the potential to inhibit CYP2C19 enzyme activity. During combination therapy with STM and CLB in patients with CYP2C19 intermediate or extensive metabolizer phenotypes, monitoring of DMCLB concentrations may be helpful in ascertaining CLB-related adverse effects.
本研究的目的是通过测定氯巴占（CLB）及其N - 去甲基氯巴占（DMCLB）的浓度与剂量（CD）比（血清水平（ng/ml）除以剂量（mg/kg）），研究舒噻美（STM）对氯巴占药代动力学的影响。我们评估了5例患者（1名成人和4名儿童），在添加或停用STM后监测其血清CLB和DMCLB浓度。5例患者中有4例为CYP2C19中间代谢型，1例为广泛代谢型。当患者服用STM（100 - 275mg/天）时，DMCLB的平均CD比增加了82.6%至248.5%，高于未使用STM时。这种增加呈剂量依赖性。相比之下，添加或停用STM后，CLB的CD比保持稳定。这些数据表明STM有可能抑制CYP2C19酶的活性。在CYP2C19中间代谢型或广泛代谢型患者中，STM与CLB联合治疗期间，监测DMCLB浓度可能有助于确定与CLB相关的不良反应。
