UGT2B7_-161C>T polymorphism associated with lamotrigine concentration-to-dose ratio

Abstract

Trabajo presentado al 9th Congress of the European Association for Clinical Pharmacology and Therepeutics celebrado en edimburgo del 12 al 15 de julio de 2009.UGT2B7 contributes to lamotrigine metabolism. The aim of this study was to analyze if there was an association between UGT2B7_-161C>T polymorphism and lamotrigine concentration-to-dose ratio (CDR) in epileptic patients. Fifty-four caucasian epileptic patients attending Neuropediatrics and Neurology Services at the Marqués de Valdecilla University Hospital, in whom lamotrigine serum concentration was to be measured for pharmacokinetic monitoring, were selected according to predefined pharmacokinetic criteria. All patients had at least one steady-state lamotrigine serum concentration obtained before the first dose in the morning. Patients were classified in three groups of co-treatment: (i) lamotrigine in combination with metabolism-inducer anticonvulsants (n = 22), (ii) lamotrigine in combination with valproate (n = 13) and (iii) lamotrigine in monotherapy or in combination with valproate and inducers (n = 16). Genotypes were determined by Applied Biosystems Genotyping Assays with TaqMan probes. The association between lamotrigine CDR and UGT2B7_-161C>T was evaluated by analysis of covariance considering the group of co-treatment and the patient age. A significant association was found between lamotrigine CDR and UGT2B7_-161C>T polymorphism (P = 0.006); lamotrigine CDR was also associated with co-treatment group (P T polymorphism might explain, at least in part, inter-patient variability in lamotrigine CDR and it should be considered besides co-treatment and patient age in the individualization of lamotrigine dose. They also show that multivariable study may be necessary in order to unmask the influence of genetic factors.Peer Reviewe