1. Effect of CYP2C19 polymorphisms on the clinical outcome of low-dose clobazam therapy in Japanese patients with epilepsy.
- Author
-
Hashi, Sachiyo, Yano, Ikuko, Shibata, Mai, Masuda, Satohiro, Kinoshita, Masako, Matsumoto, Riki, Ikeda, Akio, Takahashi, Ryosuke, and Matsubara, Kazuo
- Subjects
- *
ACADEMIC medical centers , *ANTICONVULSANTS , *CHI-squared test , *EPILEPSY , *GENETIC polymorphisms , *HIGH performance liquid chromatography , *OXIDOREDUCTASES , *RESEARCH funding , *STATISTICS , *T-test (Statistics) , *DATA analysis , *RETROSPECTIVE studies , *DATA analysis software , *DESCRIPTIVE statistics , *GENOTYPES - Abstract
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. [ABSTRACT FROM AUTHOR]
- Published
- 2015
- Full Text
- View/download PDF