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Case Reports
. 2023 Oct;13(4):434-437.
doi: 10.1177/19418744231189078. Epub 2023 Jul 10.

Elevations in Norclobazam Concentrations and Altered Mental Status in CYP2C19 Poor Metabolizer Phenotype: A Case Report

Kristy M Phillips  1 , Josanna M Rodriguez-Lopez  2 , Andrew J Webb  1
Affiliations
Case Reports

Elevations in Norclobazam Concentrations and Altered Mental Status in CYP2C19 Poor Metabolizer Phenotype: A Case Report

Kristy M Phillips et al. Neurohospitalist. 2023 Oct.

Abstract

Clobazam is a 1,5-benzodiazepine frequently used as an adjunctive agent for refractory seizures and status epilepticus. Clobazam undergoes metabolism to an active metabolite norclobazam which is subsequently hydroxylated by CYP2C19, a cytochrome with several pharmacogenetic variants. Patients with poor metabolizer phenotypes may have elevated norclobazam levels and subsequent adverse effects. We present a case of an Asian American male receiving clobazam at a standard therapeutic dose for seizure disorder who became comatose secondary to significantly elevated norclobazam concentrations. Genetic testing revealed the patient was a poor CYP2C19 metabolizer, accounting for the impaired clearance. Clinicians should be aware of the patient populations at risk for these genetic polymorphisms and adjust initial doses based on package labeling or consider therapeutic drug monitoring to avoid adverse effects.

Keywords: CYP2C19 polymorphism; case report; clobazam; norclobazam; pharmacogenomics.

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Conflict of interest statement

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Figures

Figure 1.
Figure 1.
Norclobazam concentration and GCS over time.
See this image and copyright information in PMC

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