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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Implications of pharmacogenetics for the therapeutic use of antiepileptic drugs

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Author(s):
Piana, Chiara [1] ; Antunes, Natalicia de Jesus [1] ; Della Pasqua, Oscar [1]
Total Authors: 3
Affiliation:
[1] UCL, Sch Life & Med Sci, London - England
Total Affiliations: 1
Document type: Review article
Source: EXPERT OPINION ON DRUG METABOLISM & TOXICOLOGY; v. 10, n. 3, p. 341-358, MAR 2014.
Web of Science Citations: 13
Abstract

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)

FAPESP's process: 12/18175-9 - Correlation between cerebral perfusion and pharmacokinetics of OXC and its metabolite 10-hidroxicarbazepina enantiomers in the plasma of healthy volunteers using non-linear hierarchical models
Grantee:Natalícia de Jesus Antunes
Support Opportunities: Scholarships abroad - Research Internship - Doctorate