薬理と治療

Abstract

Background and Objective The antiepileptic drug lacosamide has been approved worldwide apart from Japan and China for several years. This study evaluated the pharmacokinetics（PK）, safety, and tolerability of lacosamide following a single oral administration（100 mg, 200 mg, or 400 mg）in healthy male Japanese and Chinese subjects. Methods This study used a randomized, double-blinded, placebo-controlled, 3-way cross-over design, with 3 doses of lacosamide（100 mg, 200 mg or 400 mg）administered orally to Japanese and Chinese subjects. Primary PK parameters were the maximum plasma concentration（Cmax）, area under the plasma concentration-time curve（AUC）, and AUC from 0 to last quantifiable concentration（AUC0-t）. Pharmacogenomics of CYP2C19 and CYP2C9 were also evaluated, along with safety. Results Thirty-six subjects（18 Japanese; 18 Chinese）were enrolled and analysed in this study. Cmax, AUC, and AUC0-t were similar between Japanese and Chinese subjects. CYP2C19 mutations induced some changes in lacosamide and its main metabolite PK parameters. Increases in lacosamide AUC between CYP2C19 intermediate metabolizer vs. extensive metabolizer（EM）, and between poor metabolizer（PM）vs. EM were 10％ and 24％, respectively, suggesting that no dose reduction is required in PMs. However, dose- and body weight-normalized PK parameters for lacosamide and its main metabolite were similar in both ethnicities with the same CYP2C19 genotype. Lacosamide was well tolerated in both ethnicities. Conclusions Lacosamide showed similar PK between healthy male Japanese and Chinese subjects. Lacosamide administered at 100-400 mg orally was well-tolerated. These findings are consistent with the known PK and safety profiles in Caucasians.