The pharmacogenomics of lamotrigine (a literature review)

Abstract

Pharmacogenomics aims to optimize drug therapy with respect to genetic variations in various human genes, whose products affect drug pharmacokinetics and pharmacodynamics. Among neurological diseases, selecting effective drug therapy is especially important in epilepsy since recurrent epileptic seizures can lead to persistent epileptic brain activity and patient traumatization. Lamotrigine is a new generation broad-spectrum antiepileptic drug and is recommended as the drug of choice in focal and generalized epilepsy. By genotyping single-nucleotide polymorphisms (SNPs) associated with decreased or increased lamotrigine blood concentration, predicting the drug dose that will achieve the therapeutic serum concentration is possible. Selecting an appropriate individual drug dose avoids the development of dose-dependent side effects, which occur when the serum drug concentration is exceeded and drug discontinuation due to a lack of the expected effect because of insufficient blood levels. This review presents the results of studies of the polymorphism in genes that directly or indirectly alter lamotrigine serum levels. These include genes that encode the UGT enzymes, responsible for the conjugation and elimination of lamotrigine from the body; genes that encode transport proteins (P-glycoprotein, organic cation transporter, multidrug resistance protein, and breast cancer resistance protein); genes that encode the transcription factors HNF4 and pregnane X receptor, which regulate the expression of several liver transport proteins and enzymes. The reviewed data demonstrate the relationship between polymorphisms in these genes and changes in lamotrigine concentration.

Keywords

• epilepsy
• pharmacogenomics
• antiepileptic drugs
• lamotrigine
• single-nucleotide polymorphism