Implications of pharmacogenetics for the therapeutic use of antiepileptic drugs

Autor(es)

Piana, Chiara ^[1] ; Antunes, Natalicia de Jesus ^[1] ; Della Pasqua, Oscar ^[1]

Afiliação do(s) autor(es)

^[1] UCL, Sch Life & Med Sci, London - England

• Tipo de documento: Artigo de Revisão
• Fonte: EXPERT OPINION ON DRUG METABOLISM & TOXICOLOGY; v. 10, n. 3, p. 341-358, MAR 2014.
• Citações Web of Science: 13

Resumo

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, understanding of their clinical implication remains limited due to the lack of methodologies that discriminate the contribution of other sources of variability in CNS exposure to drugs. A model-based approach, in which other intrinsic (e.g., demographic covariates) and extrinsic (e.g., drug-drug interactions) factors are evaluated concurrently is needed to ensure optimization and individualization of treatment in epileptic patients. (AU)

• Processo FAPESP: 12/18175-9 - Correlação entre a perfusão cerebral e a farmacocinética da OXC e dos enantiômeros do seu metabólito 10-hidroxicarbazepina em plasma de voluntários sadios utilizando modelos hierárquicos não-lineares
• Beneficiário: Natalícia de Jesus Antunes
• Modalidade de apoio: Bolsas no Exterior - Estágio de Pesquisa - Doutorado