title: Interaction between sulthiame and clobazam: sulthiame inhibits the metabolism of clobazam, possibly via an action on CYP2C19.
abstract: 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.
authors.affiliation: 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. Electronic address: yamamoty-3@hosp.go.jp.
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Yamamoto
authors.affiliation: Department of Clinical Research, National Epilepsy Center, Shizuoka Institute of Epilepsy and Neurological Disorders, 886 Urushiyama, Shizuoka 420-8688, Japan.
authors.forename: Yukitoshi
authors.initials: Y
authors.lastname: Takahashi
authors.affiliation: Department of Clinical Research, National Epilepsy Center, Shizuoka Institute of Epilepsy and Neurological Disorders, 886 Urushiyama, Shizuoka 420-8688, Japan.
authors.forename: Katsumi
authors.initials: K
authors.lastname: Imai
authors.affiliation: Department of Clinical Research, National Epilepsy Center, Shizuoka Institute of Epilepsy and Neurological Disorders, 886 Urushiyama, Shizuoka 420-8688, Japan.
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Mogami
authors.affiliation: Department of Clinical Research, National Epilepsy Center, Shizuoka Institute of Epilepsy and Neurological Disorders, 886 Urushiyama, Shizuoka 420-8688, Japan.
authors.forename: Kazumi
authors.initials: K
authors.lastname: Matsuda
authors.affiliation: Department of Clinical Research, National Epilepsy Center, Shizuoka Institute of Epilepsy and Neurological Disorders, 886 Urushiyama, Shizuoka 420-8688, Japan.
authors.forename: Masahiko
authors.initials: M
authors.lastname: Nakai
authors.affiliation: Department of Clinical Pharmaceutics, Graduate School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Shizuoka 422-8526, Japan; Laboratory of Clinical Pharmacokinetics and Drug Safety, Shizuoka General Hospital, 4-27-1 Kita Ando, Shizuoka 420-8527, Japan.
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Kagawa
authors.affiliation: Department of Clinical Research, National Epilepsy Center, Shizuoka Institute of Epilepsy and Neurological Disorders, 886 Urushiyama, Shizuoka 420-8688, Japan.
authors.forename: Yushi
authors.initials: Y
authors.lastname: Inoue
mesh_terms: D000328:Adult; D000927:Anticonvulsants / Q000493:pharmacokinetics* / Q000627:therapeutic use; D001569:Benzodiazepines / Q000493:pharmacokinetics* / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D000078306:Clobazam; D065731:Cytochrome P-450 CYP2C19 / Q000378:metabolism*; D004347:Drug Interactions; D004827:Epilepsy / Q000188:drug therapy* / Q000201:enzymology; D005260:Female; D006801:Humans; D008297:Male; D013843:Thiazines / Q000493:pharmacokinetics* / Q000627:therapeutic use; D000096926:Benzenesulfonamides
chemical_list: D000927:Anticonvulsants; D001569:Benzodiazepines; D000078306:Clobazam; D065731:Cytochrome P-450 CYP2C19; D013843:Thiazines; C084593:sulthiame; D000096926:Benzenesulfonamides
keywords: CYP2C19; Clobazam; Drug interaction; Sulthiame; Therapeutic drug monitoring