Challenges and opportunities in the application of pharmacogenetics to antiepileptic drug therapy.
The recent surge of interest in pharmacogenetics has provoked considerable thought regarding its relevance to antiepileptic drug (AED) therapy. Initial studies have focused on genes whose products play a putatively important role in AED pharmacology, particularly drug transporter proteins, drug metabolizing enzymes and ion channel subunits. However, there is a lack of good correspondence between results from different laboratories, and more recent findings are awaiting attempts at confirmation. Thus, there are currently no AED treatment guidelines that are informed by pharmacogenetic data. In order to begin to have clinical impact, standards specific to the conduct of future AED studies must be established. Of particular importance are the need for accurate epilepsy classification, appropriate AED selection and clear and objective assessment outcome measures. In addition, general standards for analysis and interpretation of genetic association data must be better codified and applied consistently across studies. Finally, extensive clinical research networks must be formulated and large numbers of well characterized patients must be recruited. Further development of these critical factors will optimize chances for overcoming current challenges posed by AED pharmacogenetic research and ultimately allow the realization of improved, more rational therapeutic strategies.
Ferraro
Thomas N
TN
University of Pennsylvania, Center for Neurobiology and Behavior, Room 2209, Translational Research Laboratories, and The Children's Hospital of Philadelphia, Department of Pediatrics, Philadelphia, PA 19104, USA. TNF-@mail.med.upenn.edu
Dlugos
Dennis J
DJ
Buono
Russell J
RJ
D000818:Animals; D000927:Anticonvulsants / Q000009:adverse effects / Q000627:therapeutic use*; D004827:Epilepsy / Q000145:classification / Q000188:drug therapy* / Q000235:genetics*; D006801:Humans; D010597:Pharmacogenetics; D012640:Seizures / Q000145:classification
D000927:Anticonvulsants