GABRD promotes hepatocellular carcinoma progression via the IL-10RA/JAK2-STAT3 signaling axis.

Seizures are among the most common neurological disorders in childhood and can lead to significant morbidity and mortality if not treated promptly and effectively []. Various antiseizure medications are employed in the acute management of seizures. Diazepam, a benzodiazepine derivative, is one of the most commonly used drugs in this context []. Variability in the effectiveness and adverse effects of diazepam has been reported and may be related to the pharmacogenomic characteristics of the patients []. While some individuals achieve effective seizure control with a single dose of diazepam, others may require higher doses to attain similar results []. Additionally, the same dosage can lead to severe respiratory depression in certain patients, while others tolerate even higher doses without experiencing adverse effects []. This inconsistency in response underscores the fact that diazepam does not exert uniform effects across all patients at equivalent doses. This variability highlights the influence of pharmacogenomic factors as well as seizure semiology and the timing of the drug administration. Evidence from adult populations further supports the clinical relevance of CYP2C19 variation for diazepam outcomes. In alcohol withdrawal syndrome, CYP2C19 polymorphisms—particularly the increased-function *17 allele—have been associated with differences in diazepam exposure and variable treatment response and tolerability, highlighting clinically meaningful inter-individual variability in real-world use; although the clinical context differs from pediatric convulsive status epilepticus, these findings provide a rationale for investigating CYP2C19-driven variability in acute benzodiazepine treatment [, ]. Pharmacokinetic/pharmacogenetic studies further support biological plausibility. Zubiaur et al. demonstrated an association between CYP2C19 phenotype and diazepam exposure and also underscored that additional metabolic pathways (e.g., CYP2B6) may contribute to diazepam pharmacokinetic variability []. Diazepam pharmacogenetics is largely influenced by functional variation in CYP2C19, a key enzyme involved in its biotransformation [, ]. Reduced-function alleles such as CYP2C19 *2/*3 may decrease clearance and prolong drug effects, whereas the increased-function allele CYP2C19*17 is associated with faster clearance and variable clinical response []. Accordingly, CYP2C19 genotype can contribute to inter-individual differences in diazepam efficacy and the risk of adverse effects, including respiratory depression [, ].