An Original Investigation into the Role of Pharmacogenomics in Antiepileptic Drug Response Variability in Nigerian Patients

Antiepileptic drug response variability in Nigerian patients is attributable to multiple factors including pharmacokinetic and pharmacodynamic genetic determinants that have not been systematically characterised in the Nigerian population context. This study conducted an original investigation into the contribution of pharmacogenomic variation to antiepileptic drug response variability in patients with epilepsy in Nigeria. A prospective pharmacogenomics-pharmacokinetics-pharmacodynamics study was conducted at neurological units at teaching hospitals in Sokoto, Plateau, and Lagos States, enrolling 150 adult patients with new-onset epilepsy initiated on carbamazepine or sodium valproate. Genotyping for CYP2C9, CYP2C19, SCN1A, ABCB1 (P-glycoprotein), and HLA-B alleles was performed using a validated next-generation sequencing panel. Drug plasma concentrations were measured at steady-state, and seizure freedom at 12 months was the primary pharmacodynamic endpoint. Population pharmacokinetic models were fitted to the data, and pharmacogenomic variants were incorporated as covariates. Results demonstrated that CYP2C9*3 variant carriers showed significantly higher carbamazepine exposure (AUC 2.3-fold increase; p < 0.001) and higher rates of adverse drug reactions. SCN1A polymorphisms were associated with differential sodium valproate response. HLA-B*15:02 screening identified carriers at risk for carbamazepine-induced Stevens-Johnson Syndrome in 4.7 percent of enrolled patients, none of whom had been screened prior to initiation. The study constitutes Nigeria's first comprehensive pharmacogenomics-integrated antiepileptic drug response investigation and provides genotype-informed prescribing recommendations specific to the Nigerian population. Keywords: pharmacogenomics, antiepileptic drugs, epilepsy, CYP2C9, Nigerian population