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 Ribeirão 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.
Subject(s)
Humans , Male , Female , Adult , Middle Aged , Aged , Aged, 80 and over , Drug Interactions/immunology , Anticonvulsants/analysis , Drug Therapy/statistics & numerical data , Drug Resistant Epilepsy/drug therapyABSTRACT
Objective: to review the experience with lamotrigine therapeutic drug monitoring in a tertiary epilepsy centre aiming to characterize the plasma concentrations profile. Methods: inclusion of adults and children to whom lamotrigine concentrations were requested from October 2008 to April 2010. A chromatographic method was validated to determine lamotrigine concentrations. Reference range adopted (plasma): 2.5-15.0 mg/L. Results: 115 patients were included (86 adults, 29 children). Mean±standard deviation lamotrigine dosages for adults and children were statistically different (5.1±2.0 versus 7.4±3.4 mg/kg/day respectively, p<0.0001), so as lamotrigine concentrations (5.13±4.0 versus 9.0±5.6 mg/L respectively, p=0.0006). Approximately 68% of all quantifications were within the reference range. From the 29 quantifications below 2.5 mg/L, 27 corresponded to lamotrigine+enzyme inducers therapies. There was no correlation between lamotrigine concentrations and dosages neither for pediatric nor for adult groups. Patients on monotherapy had lamotrigine concentrations significantly higher than those on lamotrigine+inducers therapies (p<0.001), and patients on lamotrigine+valproic acid therapy had lamotrigine concentrations higher than those on lamotrigine+inducers (p<0.001). There was no significant difference among mean dosages according to different comedications. Conclusion: our observations about the influence of polytherapies on lamotrigine pharmacokinetics confirm the relevance of quantifying this antiepileptic drug plasma concentrations in the process of treatment optimization...
Objetivo: revisar a experiência de um centro terciário de epilepsia com a monitorização terapêutica da lamotrigina objetivando caracterizar o perfil de concentrações plasmáticas encontradas. Métodos: inclusão de todos adultos e crianças para os quais solicitou-se quantificação plasmáticas de lamotrigina de Outubro/2008 a Abril/2010. Um método cromatográfico foi validado para determinar as concentrações de lamotrigina. Intervalo de referência adotado (plasma): 2.5-15.0 mg/L. Resultados: 115 pacientes foram incluídos (86 adultos, 29 crianças). Média±desvio-padrão das doses de lamotrigina para adultos e crianças foram significativamente diferentes (5.1±2.0 versus 7.4±3.4 mg/kg/dia respectivamente, p<0.0001), assim como as concentrações (5.13±4.0 versus 9.0±5.6 mg/L, p=0.0006). Aproximadamente 68% das quantificações estavam dentro do intervalo de referência. Das 29 quantificações abaixo de 2.5 mg/L, 27 correspondiam a associações lamotrigina+indutores enzimáticos. Não houve correlação entre concentrações e doses de lamotrigina. Pacientes em monoterapia tiveram concentrações de lamotrigina significativamente maiores do que pacientes utilizando lamotrigina+indutores enzimáticos (p<0.001); pacientes em uso de lamotrigina+ácido valproico apresentaram concentrações maiores comparativamente àqueles em uso de lamotrigina+indutores (p<0.001). Não houve diferença significativa entre doses médias de acordo com diferentes comedicações. Conclusão: a influência de politerapias sobre a farmacocinética da lamotrigina confirma a relevância dese quantificar as concentrações plasmáticas deste antiepilético no processo de otimização terapêutica...