Dataset Information

Topiramate dosage optimization for effective antiseizure management via population pharmacokinetic modeling.

ABSTRACT:

Objective

Despite the suggested topiramate serum level of 5-20 mg/L, numerous institutions have observed substantial drug response at lower levels. We aim to investigate the correlation between topiramate serum levels, drug responsiveness, and adverse events to establish a more accurate and tailored therapeutic range.

Methods

We retrospectively analyzed clinical data collected between January 2017 and January 2022 at Seoul National University Hospital. Drug responses to topiramate were categorized as "insufficient" or "sufficient" by reduction in seizure frequency ≥ 50%. A population pharmacokinetic model estimated serum levels from spot measurements. ROC curve analysis determined the optimal cutoff values.

Results

A total of 389 epilepsy patients were reviewed having a mean dose of 178.4 ± 117.9 mg/day and the serum level, 3.9 ± 2.8 mg/L. Only 5.6% samples exhibited insufficient response, with a mean serum level of 3.6 ± 2.5 mg/L while 94.4% demonstrated sufficient response, with a mean 4.0 ± 2.8 mg/L, having no statistical significance. Among the 69 reported adverse events, logistic regression analysis identified a significant association between ataxia and serum concentration (p = 0.04), with an optimal cutoff value of 6.5 mg/L.

Interpretation

This study proposed an optimal therapeutic concentration for topiramate based on patients' responsiveness to the drug and the incidence of adverse effects. We recommended serum levels below 6.5 mg/L to mitigate the risk of ataxia-related side effects while dose elevation was found unnecessary for suboptimal responders, as the drug's effectiveness plateaus at minimal doses.

SUBMITTER: Lee S

PROVIDER: S-EPMC10863906 | biostudies-literature | 2024 Feb

REPOSITORIES: biostudies-literature

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Publications

Topiramate dosage optimization for effective antiseizure management via population pharmacokinetic modeling.

Lee Seolah S Kim Hyun Chul HC Jang Yoonhyuk Y Lee Han Sang HS Ahn Seon-Jae SJ Lee Soon-Tae ST Jung Keun-Hwa KH Park Kyung-Il KI Jung Ki-Young KY Oh Jaeseong J Lee SeungHwan S Yu Kyung-Sang KS Jang In-Jin IJ Lee Soyoung S Chu Kon K Lee Sang Kun SK

Annals of clinical and translational neurology 20231207 2

<h4>Objective</h4>Despite the suggested topiramate serum level of 5-20 mg/L, numerous institutions have observed substantial drug response at lower levels. We aim to investigate the correlation between topiramate serum levels, drug responsiveness, and adverse events to establish a more accurate and tailored therapeutic range.<h4>Methods</h4>We retrospectively analyzed clinical data collected between January 2017 and January 2022 at Seoul National University Hospital. Drug responses to topiramate ...[more]

PMID: 38062636

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Dataset Information

Topiramate dosage optimization for effective antiseizure management via population pharmacokinetic modeling.

Objective

Methods

Results

Interpretation

Publications

Topiramate dosage optimization for effective antiseizure management via population pharmacokinetic modeling.

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