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Intravenous diazepam application in a departmental convulsive status epilepticus protocol with CYP2C19 polymorphisms:

Muazzez Seker Gezici1,2, Caner Turan3, Durdugul Ayyildiz Emecen4

  • 1Department of Pediatrics, Ege University Faculty of Medicine, Izmir, Turkey. meceseker@gmail.com.

BMC Pharmacology & Toxicology
|June 5, 2026
PubMed

Insights

Genetic variations in CYP2C19 influence how children respond to diazepam for seizures. Specific CYP2C19 genotypes, like CYP2C19*17 CT/TT combined with CYP2C19*2 GG, predict treatment failure and respiratory risks in pediatric patients.

Area of Science:

  • Pharmacogenetics
  • Clinical Pharmacology
  • Pediatric Neurology

Background:

  • Diazepam response varies significantly in children, potentially due to genetic differences in its metabolism.
  • Cytochrome P450 2C19 (CYP2C19) is a key enzyme in diazepam metabolism, and its genetic polymorphisms may explain individual variability.

Purpose of the Study:

  • To investigate the association between specific CYP2C19 genetic polymorphisms (*2, *3, and *17) and the efficacy and safety of intravenous diazepam in pediatric seizure patients.
  • To determine if CYP2C19 genotype influences treatment outcomes, including seizure control and respiratory adverse effects.

Main Methods:

  • A prospective cohort study involving 100 pediatric patients (0-18 years) treated with IV diazepam for seizures.
  • Next-generation sequencing was used for CYP2C19 genotyping (*2, *3, *17).
  • Clinical outcomes assessed included seizure cessation after one or two diazepam doses and the incidence of respiratory complications.

Main Results:

  • Seizure cessation was achieved in 76% with the first IV diazepam dose and 79% overall. Respiratory side effects occurred in 15% of patients.
  • CYP2C19*2 and CYP2C19*17 alleles were present in 19% and 49% of participants, respectively; CYP2C19*3 was absent.
  • The CYP2C19*17 CT/TT genotype, especially with CYP2C19*2 GG, was significantly linked to diazepam treatment failure (p=0.038) and increased respiratory adverse effects (p=0.005).

Conclusions:

  • This is the first study to link CYP2C19 polymorphisms to diazepam treatment outcomes in Turkish children with seizures.
  • Pharmacogenetic profiling of CYP2C19 may help predict diazepam efficacy and safety, improving benzodiazepine use in pediatric seizure management.
Abstract

Keywords:
Antiseizure drugsCYP2C19Genetic polymorphismPharmacogeneticsSeizures

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