Aims: Despite the large number of antiepileptic drugs (AED) currently on the market, in 20-30% of patients it is still not possible to achieve a total control of the seizures or to prevent the appearance of idiosyncratic side effects.
Development: In this study the pharmacokinetic and pharmacodynamic factors involved in pharmacoresistance in epilepsies are analysed, with special attention given to the polymorphisms of metabolising enzymes or their inducers, particularly the hepatic cytochrome CYP, the over-expression of membrane-transporting proteins -P-glycoprotein (PGP), MRP- and polymorphisms in the ion channels. Idiosyncratic effects are produced due to an imbalance between the production of toxic metabolites and the individual capacity to detoxify them. Pharmacogenetics and pharmacogenomics can identify certain personal, biochemical, enzymatic and genetic characteristics that are of use in selecting the most effective AED with the lowest risk of idiosyncratic effects for each person.
Conclusions: Although new AED that can help reduce the number of medication resistant patients must be introduced, at the same other therapeutic strategies have to be developed with the aid of pharmacogenomics; more specifically there is a need for AED that are not transported by PGP o MRP, or substances that antagonise those membrane transporters and make it possible for the AED to reach the site where they are to act. Furthermore, the detoxification capacity of each individual must be known in order to be able to minimise the risk of idiosyncratic side effects.