Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
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.

PubMed Disclaimer

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

References

    1. Sankar R. GABAA receptor physiology and Its relationship to the mechanism of action of the 1,5-benzodiazepine clobazam. CNS Drugs. 2012;26(3):229-244. doi:10.2165/11599020-000000000-00000 - DOI - PubMed
    1. Bardy AH, Seppälä T, Salokorpi T, Granström ML, Santavuori P. Monitoring of concentrations of clobazam and norclobazam in serum and saliva of children with epilepsy. Brain Dev. 1991;13(3):174-179. doi:10.1016/S0387-7604(12)80025-8 - DOI - PubMed
    1. Rupp W, Badian M, Christ O, et al. Pharmacokinetics of single and multiple doses of clobazam in humans. Br J Clin Pharmacol. 1979;7(Suppl 1):51S-57S. - PMC - PubMed
    1. Kosaki K, Tamura K, Sato R, Samejima H, Tanigawara Y, Takahashi T. A major influence of CYP2C19 genotype on the steady-state concentration of N-desmethylclobazam. Brain Dev. 2004;26(8):530-534. doi:10.1016/j.braindev.2004.02.010 - DOI - PubMed
    1. Seo T, Nagata R, Ishitsu T, et al. Impact of CYP2C19 polymorphisms on the efficacy of clobazam therapy. Pharmacogenomics. 2008;9(5):527-537. doi:10.2217/14622416.9.5.527 - DOI - PubMed

Publication types

LinkOut - more resources