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タイトル: Effect of CYP2C19 polymorphisms on the clinical outcome of low-dose clobazam therapy in Japanese patients with epilepsy.
著者: Hashi, Sachiyo
Yano, Ikuko
Shibata, Mai
Masuda, Satohiro
Kinoshita, Masako
Matsumoto, Riki
Ikeda, Akio
Takahashi, Ryosuke
Matsubara, Kazuo
著者名の別形: 矢野, 育子
キーワード: Clobazam
N-Desmethylclobazam
CYP2C19 poor metabolizer
Low-dose therapy
Therapeutic drug monitoring
発行日: 18-Oct-2014
出版者: Springer Berlin Heidelberg
誌名: European journal of clinical pharmacology
巻: 71
号: 1
開始ページ: 51
終了ページ: 58
抄録: [Purpose]Clobazam (CLB) is metabolized by cytochrome P450 (CYP) 3A4 to yield N-desmethylclobazam (N-CLB), which is further inactivated by CYP2C19. The aim of this study was to retrospectively evaluate the relationship between CYP2C19 polymorphisms and the efficacy of low-dose, add-on CLB therapy in Japanese patients with epilepsy. [Methods]Fifty patients were divided into three groups according to their CYP2C19 polymorphism. CLB and N-CLB serum concentrations and seizure frequency before and after starting CLB were analyzed. [Results]Extensive metabolizers (EMs, n = 11), intermediate metabolizers (IMs, n = 22), and poor metabolizers (PMs, n = 17) were included. Although the dose-normalized CLB serum concentrations were not significantly different, the dose-normalized N-CLB serum concentrations were significantly higher in PMs than in EMs or IMs. Seizure frequency was significantly decreased by the CLB therapy in PMs (p < 0.01), but not in EMs or IMs. CLB serum concentrations did not correlate with seizure reduction rate, but median N-CLB serum concentrations were significantly higher in patients with excellent seizure control (≧90 % seizure reduction) compared to those with ≧50 % seizure reduction or with <50 % seizure reduction (1103, 341, and 570 ng/mL, respectively). [Conclusions]The efficacy of low-dose CLB therapy was significantly influenced by CYP2C19 polymorphisms. Ideally, CLB therapy should be started with a low dose (2.5 mg/day) and dosage increased until N-CLB serum concentration reaches 1100 ng/mL or until the desired effect is acquired, a recommendation that is particularly important for PMs.
著作権等: The final publication is available at Springer via http://dx.doi.org/10.1007/s00228-014-1773-z.
The full-text file will be made open to the public on 18 October 2015 in accordance with publisher's 'Terms and Conditions for Self-Archiving'.
This is not the published version. Please cite only the published version. この論文は出版社版でありません。引用の際には出版社版をご確認ご利用ください。
URI: http://hdl.handle.net/2433/200178
DOI(出版社版): 10.1007/s00228-014-1773-z
PubMed ID: 25323806
出現コレクション:学術雑誌掲載論文等

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