The interface of preclinical evaluation with clinical testing of antiepileptic drugs: role of pharmacogenomics and pharmacogenetics.
Despite the release of eight antiepileptic drugs (AEDs) during the last decade, the incidence of pharmacoresistant epilepsy has changed relatively little. Predicting efficacy and safety of AEDs in people with epilepsy from acute seizure models in rodents is difficult and risky. It is becoming increasingly clear that genetic polymorphisms play an integral role in variability in both antiepileptic drug pharmacokinetics and pharmacodynamics. The publication of the human genome and increasing sophisticated and powerful genetic tools offers new methods for screening drugs and predicting deadly idiosyncratic side effects. In this review the use of pharmacogenomic and pharmacokinetic techniques in the development and monitoring of antiepileptic drug therapy is reviewed. Genetic techniques have the potential of identifying novel drug targets, predicting drug response, and identifying individuals at risk for serious idosyncratic reactions.
Holmes
Gregory L
GL
Clinical Neurophysiology Laboratory, Department of Neurology, Harvard Medical School, Center for Research in Pediatric Epilepsy, Children's Hospital Boston, Hunnewell 2, 300 Longwood Avenue, Boston, MA 02115, USA. gregory.holmes@tch.harvard.edu
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology* / Q000633:toxicity; D004353:Drug Evaluation, Preclinical; D004827:Epilepsy / Q000188:drug therapy* / Q000235:genetics*; D023281:Genomics; D006801:Humans; D010597:Pharmacogenetics; D011110:Polymorphism, Genetic / Q000235:genetics
D000927:Anticonvulsants