Implications of pharmacogenetics for the therapeutic use of antiepileptic drugs

Introduction: Epilepsy is a chronic neurological disease manifesting as recurrent seizures. Despite the availability of numerous antiepileptic drugs (AEDs), one-third of the patients are not responsive to treatment. Such inter-individual variability in the response to AEDs may be partly explained by genetic differences. This review summarizes the pharmacogenetics (PGx) of AEDs. In addition, a model-based approach is presented that enables the integration of PGx data with other relevant sources of variability, such as demographic characteristics and co-medications. Areas covered: A comprehensive overview is provided of the data available in the literature on the evidence for correlations between genetic mutations and pharmacokinetic (PK) and/or pharmacodynamics (PD) of AEDs. This information is then used in an integrated manner in the second part, where PGx differences are parameterized as covariates in PK and PKPD models. Expert opinion: Polymorphisms are profuse in the PK and PD of AEDs. However, underst...