Eur J Clin Pharmacol (2015) 71:51–58 DOI 10.1007/s00228-014-1773-z
PHARMACOGENETICS
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
Received: 2 September 2014 / Accepted: 9 October 2014 / Published online: 18 October 2014 # Springer-Verlag Berlin Heidelberg 2014
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 lowdose, 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. S. Hashi : I. Yano : M. Shibata : S. Masuda : K. Matsubara Department of Clinical Pharmacology and Therapeutics, Kyoto University Hospital, Sakyo-ku, Kyoto 606-8507, Japan I. Yano (*) : M. Shibata Department of Clinical Pharmacy and Education, Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan e-mail: [email protected] M. Kinoshita Department of Neurology, Utano National Hospital, National Hospital Organization, Ukyo-ku, Kyoto 616-8255, Japan R. Matsumoto : A. Ikeda : R. Takahashi Department of Neurology, Graduate School of Medicine, Kyoto University, Sakyo-ku, Kyoto 606-8507, Japan Present Address: R. Matsumoto : A. Ikeda Department of Epilepsy, Movement Disorders and Physiology, Graduate School of Medicine, Kyoto University, Sakyo-ku, Kyoto 606-8507, Japan Present Address: S. Masuda Department of Pharmacy, Kyushu University Hospital, Maidashi, Higashi-ku, Fukuoka 812-8582, Japan
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
PHARMACOGENETICS
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
Received: 2 September 2014 / Accepted: 9 October 2014 / Published online: 18 October 2014 # Springer-Verlag Berlin Heidelberg 2014
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 lowdose, 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. S. Hashi : I. Yano : M. Shibata : S. Masuda : K. Matsubara Department of Clinical Pharmacology and Therapeutics, Kyoto University Hospital, Sakyo-ku, Kyoto 606-8507, Japan I. Yano (*) : M. Shibata Department of Clinical Pharmacy and Education, Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan e-mail: [email protected] M. Kinoshita Department of Neurology, Utano National Hospital, National Hospital Organization, Ukyo-ku, Kyoto 616-8255, Japan R. Matsumoto : A. Ikeda : R. Takahashi Department of Neurology, Graduate School of Medicine, Kyoto University, Sakyo-ku, Kyoto 606-8507, Japan Present Address: R. Matsumoto : A. Ikeda Department of Epilepsy, Movement Disorders and Physiology, Graduate School of Medicine, Kyoto University, Sakyo-ku, Kyoto 606-8507, Japan Present Address: S. Masuda Department of Pharmacy, Kyushu University Hospital, Maidashi, Higashi-ku, Fukuoka 812-8582, Japan
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
