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Original Articles
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Journal of K orean Epilepsy Society 2013 June;17(1):1-7.
Published online 2013 October 14
Copyright ⓒ 2010 Journal of Korean Epilepsy Society
뇌전증지속상태에서 토피라메이트의 치료약물농도
구대림4*⋅서수연3*⋅김대영5⋅홍승봉6⋅주은연6⋅이수연1,2
성균관대학교 의과대학 삼성서울병원 1진단검사의학과, 2임상약리학과, 3경기여자고등학교, 4서울대학교 의과대학 보라매병원 신경과, 5충남대학교 의과대학 충남대병원 신경과, 6성균관대학교 의과대학 삼성서울병원 신경과
Corresponding Author: Soo-Youn Lee, MD ,Tel: +82-2-3410-1834, Fax: +82-2-3410-2719, Email: suddenbz@skku.edu
ABSTRACT
Purpose: Status epilepticus (SE) is a pathologic state where pharmacokinetic alterations can be more pronounced and more rapid than during the other epileptic states. The consequences of such changes can exert negative influences on the timely adequate treatments for stopping uncontrolled seizures during SE. Topiramte (TPM) is one of new antiepileptic drugs with high efficacy in epilepsy, which can also be effectively used in SE. The aim of this study was to evaluate the pharmacokinetic changes during the SE by an analysis of the therapeutic drug monitoring (TDM) of TPM in patients with SE.
Methods: We retrospectively analyzed 49 serum measurements of TPM from 22 subjects with SE. The serum concentrations of TPM were measured by HPLC-tandem mass spectrometry. TDM data were categorized into malignant status epilepticus (MSE), refractory status epilepticus (RSE), and non-status epilepticus (NSE) groups. We compared concentration-to-dose ratio (CDR) among those groups.
Results: Among 49 cases, 11 were in MSE, 19 in RSE, and 19 in NSE. The daily dose of TPM was higher in MSE (median, interquartile range: 600, 600-800 mg) than in RSE (300, 250-600 mg) and NSE (200, 150-400 mg). The daily dose adjusted for body weight was also higher in MSE (12.2, 10.4-13.9 mg/kg) than in RSE (4.5, 3.8-12.2 mg/kg) and NSE (4.1, 2.3-7.1 mg/kg) (p<0.01). Serum concentrations of TPM were less in MSE (5.8, 4.2-7.3 mg/L) and RSE (4.9, 2.9-6.0 mg/L) than in NSE (5.5, 3.3-9.0 mg/L), which were not significantly different among the groups (p>0.1). However, the concentrationto- dose ratio (CDR) was significantly lower in MSE (0.41, 0.35-0.59 kg/L) and RSE (0.85, 0.39-1.23 kg/L) than in NSE (1.72, 0.96-2.24 kg/L) (post hoc analysis, p<0.005, 0.05).
Conclusions: The serum concentrations of TPM can be influenced by SE, particularly in MSE. The higher range of dose of TPM could be needed for an adequate treatment of SE.
Keywords: Status epilepticus, Topiramate, Therapeutic drug monitoring

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