Effect of CYP2C19 polymorphisms on the clinical outcome of low-dose clobazam therapy in Japanese patients with epilepsy

Sachiyo Hashi, Ikuko Yano, Mai Shibata, Satohiro Masuda, Masako Kinoshita, Riki Matsumoto, Akio Ikeda, Ryosuke Takahashi, Kazuo Matsubara

研究成果: Contribution to journalArticle

13 被引用数 (Scopus)

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 (蠇90 % seizure reduction) compared to those with 蠇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.

本文言語英語
ページ(範囲)51-58
ページ数8
ジャーナルEuropean Journal of Clinical Pharmacology
71
1
DOI
出版ステータス出版済み - 1 2015

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmacology (medical)

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