J Korean Epilepsy Soc.  2013 Jun;17(1):1-7.

Therapeutic Drug Monitoring of Topiramate in Status Epilepticus

• Koo DL
• Seo S
• Kim D
• Hong SB
• Joo EY
• Lee SY

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 concentration-to-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.

Keyword

Status epilepticus; Topiramate; Therapeutic drug monitoring

MeSH Terms

Anticonvulsants
Body Weight
Drug Monitoring
Epilepsy
Fructose
Humans
Mass Spectrometry
Retrospective Studies
Seizures
Status Epilepticus
Anticonvulsants
Fructose