The relationship between the pharmacology of antiepileptic drugs and human gene variation: An overview

Thomas N. Ferraro, Russell J. Buono

Research output: Contribution to journalReview articlepeer-review

49 Scopus citations

Abstract

Individual differences in clinical responsiveness to antiepileptic drugs are due to a complex interaction between environmental factors and genetic variation. Considerable interest has arisen in exploiting advances in molecular genetics to improve drug therapy for epilepsy and many other diseases; however, practical application of pharmacogenetics has been difficult to realize. Attempts to define gene variants that are associated with therapeutic (or adverse) effects of antiepileptic drugs rely currently on the prior identification of candidate genes and the subsequent evaluation of the distribution of allelic variants between individuals who have a "good" versus a "poor" clinical response. Many factors can adversely affect interpretation of such data, and careful consideration must be given to the design of genetic association studies involving candidate genes. Candidate genes may be identified in a number of ways; however, for studies of drugs, application of knowledge derived from basic pharmacology can suggest focused and testable hypotheses that are based on the fundamental principles of drug action. Thus, studies of genetic variation as they relate to proteins involved in antiepileptic drug kinetics and dynamics will identify key polymorphisms in endogenous molecules that determine degrees of drug efficacy and toxicity. Delineation of these effects in the coming years will promote enhanced success in the treatment of epilepsy.

Original languageEnglish (US)
Pages (from-to)18-36
Number of pages19
JournalEpilepsy and Behavior
Volume7
Issue number1
DOIs
StatePublished - Aug 2005
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Neurology
  • Clinical Neurology
  • Behavioral Neuroscience

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