Influence of the clinical profile of patients with refractory epilepsy on lamotrigine plasma concentration

André Oliveira Baldoni,Priscila Freitas-Lima,Veriano Alexandre,Edson Zangiacomi Martinez,Leonardo Regis Leira Pereira,Americo Ceiki Sakamoto,Regina Helena Costa Queiroz,Flávia Isaura De Santi Ferreira

doi:10.1590/s2175-97902018000200246

Abstract

ABSTRACT The purpose of this work was to evaluate the influence of the clinical profile on lamotrigine (LTG) plasma concentrations from patients with refractory epileptic seizures. In this cross-sectional study, therapeutic monitoring of LTG, and questionnaires with 75 patients with refractory epileptic seizures of a Hospital in Ribeirao Preto-SP-Brazil were performed. The multiple linear regression model was used to verify association between the LTG plasma concentrations and the independent variables. Covariance analysis was used to compare the mean LTG plasma concentration among the co-medication groups. The LTG plasma concentration was associated both with the LTG dosage (mg/kg/day) (p=0.0096) and with the use of first generation antiepileptic drugs (AED) (p<0.01), being carbamazepine (CBZ) and phenytoin (PHT), the AEDs showing the most prominent influence in reducing LTG plasma concentrations. Adverse events, adherence to the pharmacological treatment, and epileptic seizures frequency, did not show significant correlation with LTG plasma concentration values. The conclusion is that LTG plasma concentration is significantly influenced by the LTG dosage and by the concomitant use of a first generation AED.

Highlights

Drug therapy is the first choice for epilepsy treatment in the majority of cases
Monotherapy is usually considered as the initial strategy, and despite 47% of patients having their seizures under control with only one antiepileptic drug (AED), 13% will require the association of a second AED to suppress the seizure recurrence
The performance of the multiple linear regression model to assess any possible association between LTG plasma concentrations and clinical and/or pharmacotherapeutic variables highlighted that only LTG dosage was significantly associated with LTG plasma concentration values (p=0.0096) (Table II)

Summary

Introduction

Drug therapy is the first choice for epilepsy treatment in the majority of cases. Monotherapy is usually considered as the initial strategy, and despite 47% of patients having their seizures under control with only one antiepileptic drug (AED), 13% will require the association of a second AED to suppress the seizure recurrence. 40% of the patients will continue to experience epileptic seizures in spite of adequate drug therapy, eventually being regarded as patients with refractory epileptic seizures (Kwan, Brodie, 2000; 2003). In this context, lamotrigine (LTG) is an AED widely prescribed in association both with first and/or second generation AEDs, which favors the possible occurrence of drug interactions, since its metabolism is known to be influenced by different AEDs (Reinsberger, Dorn, Krämer, 2008; Johannessen, Landmark, 2010). In addition to factors related to pharmacotherapy, there are other clinical, physiological, pathological and even demographic factors influencing the pharmacokinetic of LTG (Reinsberger, Dorn, Krämer, 2008; Patsalos et al, 2008)

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