Interchangeability among therapeutic equivalents of lamotrigine: evaluation of quality of life

Epilepsia é o distúrbio neurológico grave mais comum no mundo todo. Aproximadamente 70% dos pacientes com epilepsia têm suas crises controladas com tratamento clínico e farmacológico. Esta pesquisa avaliou a possível interferência da intercambialidade entre equivalentes terapêuticos da lamotrigina na condição clínica e na qualidade de vida dos pacientes com epilepsia refratária. O estudo foi dividido em três períodos de 42 dias e em cada período foi dispensado um equivalente terapêutico, aleatoriamente (dois similares - formulação A e B e o medicamento de referência - formulação C). A dose média de lamotrigina foi de 5,5 mg/kg/dia. A ocorrência de efeitos colaterais tende a ser mais decisiva para a redução da qualidade de vida em epilepsia refratária em relação às variações no número de crises ou alterações nas concentrações plasmáticas. Os resultados demonstram que, independentemente do medicamento prescrito, a intercambialidade entre equivalentes terapêuticos pode interferir no sucesso do controle da epilepsia.Epilepsy is the most common serious neurological disorder worldwide. Approximately 70% of patients with epilepsy have their seizures controlled by clinical and pharmacological treatment. This research evaluated the possible influence of interchangeability among therapeutic equivalents of LTG on the clinical condition and quality of life of refractory epileptic patients. The study was divided into three periods of 42 days, and an equivalent therapeutic LTG randomly dispensed for each period (two similars - formulations A and B, and the reference product - formulation C). The mean dose of LTG was 5.5 mg/kg/day. The presence of side effects tends to have a greater deleterious effect on quality of life of refractory epileptics compared to variations in number of seizures or changes in plasma concentrations. The results showed that independently of the drug prescribed, interchangeability among therapeutic equivalents can negatively impact epilepsy control

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

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

Stir bar-sorptive extraction, solid phase extraction and liquid-liquid extraction for levetiracetam determination in human plasma: comparing recovery rates

Levetiracetam (LEV), an antiepileptic drug (AED) with favorable pharmacokinetic profile, is increasingly being used in clinical practice, although information on its metabolism and disposition are still being generated. Therefore a simple, robust and fast liquid-liquid extraction (LLE) followed by high-performance liquid chromatography method is described that could be used for both pharmacokinetic and therapeutic drug monitoring (TDM) purposes. Moreover, recovery rates of LEV in plasma were compared among LLE, stir bar-sorptive extraction (SBSE), and solid-phase extraction (SPE). Solvent extraction with dichloromethane yielded a plasma residue free from usual interferences such as commonly co-prescribed AEDs, and recoveries around 90% (LLE), 60% (SPE) and 10% (SBSE). Separation was obtained using reverse phase Select B column with ultraviolet detection (235 nm). Mobile phase consisted of methanol:sodium acetate buffer 0.125 M pH 4.4 (20:80, v/v). The method was linear over a range of 2.8-220.0 µg mL-1. The intra- and inter-assay precision and accuracy were studied at three concentrations; relative standard deviation was less than 10%. The limit of quantification was 2.8 µg mL-1. This robust method was successfully applied to analyze plasma samples from patients with epilepsy and therefore might be used for pharmacokinetic and TDM purposes.</p

Towards sustainability in European agricultural firms

Agricultural activity plays an important role in all 28 Member States (MS) of the European Union (EU) in terms of: -Economics, -Environmental, -Social, and -Political activity. The sector also provides: -agricultural goods and services to support food security; -exports and imports at European and World level; -creation of direct and indirect jobs; and -the maintenance of population living in rural and regional areas.N/

Qualidade de vida e eventos adversos de pacientes com epilepsia farmacorresistente em uso de lamotrigina

Study design: Cross-sectional study. Introduction: Pharmacological treatment is the first option to treat epilepsy, and about 40% of patients require polytherapy to better control epileptic seizures, which may be associated with an increase in adverse events and impairment of quality of life. Objective: To evaluate the quality of life of patients with pharmacoresistant epilepsy using lamotrigine (LTG), as well as to verify the association of adverse events with antiepileptic drugs with quality of life. Methods: This cross-sectional study was carried out with 75 patients with drugresistant epilepsy using LTG, in a Clinic of Epilepsy of Difficult Control of Ribeirão Preto-SP, from May/2011 to April / 2012. The clinical variables analyzed were Quality of Life in Epilepsy (QOLIE31) and the Adverse Events Profile Questionnaire (AEP). Socio-demographic and pharmacotherapeutic data were collected through patient records. This study was approved by the Research Ethics Committee of the General Hospital of the Medical School of Ribeirão Preto of the University of São Paulo (HCFMRP-USP), whose case number is 8791/2010. Results: The most frequent adverse events were somnolence and difficulty concentrating. In addition, low scores were observed in all domains related to quality of life (Qolie-31). Conclusion: Quality of life has an inverse association with adverse events in patients using antiepileptic drugs (p &lt;0.01).Modelo do estudo: Estudo transversal. Introdução: O tratamento farmacológico é a primeira opção para o tratamento da epilepsia, e cerca de 40% dos pacientes necessitam de politerapia para melhor controle das crises epilépticas, o que pode estar associado ao aumento de eventos adversos e comprometimento da qualidade de vida. Objetivos: Avaliar a qualidade de vida de pacientes com epilepsia farmacoresistente em uso de lamotrigina (LTG), bem como verificar a associação dos eventos adversos dos antiepilépticos com a qualidade de vida. Metodologia: Este estudo transversal foi realizado com 75 pacientes com epilepsia farmacorresistente em uso LTG atendidos em um Ambulatório de Epilepsia de Difícil Controle de Ribeirão Preto-SP, no período de maio/2011 a abril/2012. As variáveis clínicas analisadas foram a qualidade de vida (Quality of Life in Epilepsy - Qolie-31) e o perfil de eventos adversos (AEP – Adverse Events Profile Questionnaire). Dados sociodemográficos e farmacoterapêuticos foram coletados através dos prontuários dos pacientes. Este trabalho foi aprovado pelo Comitê de Ética em Pesquisa do Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo (HCFMRP-USP), cujo número do processo é 8791/2010. Resultados: Os eventos adversos mais frequentes foram sonolência e dificuldade de concentração. Além disso, observou-se baixos escores em todos os domínios relacionados à qualidade de vida (Qolie-31). Conclusão: A qualidade de vida possui associação inversamente significativa com os eventos adversos, nos pacientes em uso de antiepilépticos (p&lt;0,01)

Validation of the Subjective Handicap of Epilepsy (SHE) in Brazilian patients with epilepsy

The objectives of the study were to translate and adapt the Subjective Handicap of Epilepsy (SHE) instrument to Brazilian Portuguese and to determine its psychometric properties for the evaluation of quality of life in patients with epilepsy. A sample of 448 adult patients with epilepsy with different clinical profiles (investigation, preoperative period, postoperative period, and drug treatment follow-up) was evaluated with the SHE and the Epilepsy Surgery Inventory (ESI-55). Exploratory factorial analysis demonstrated that four factors explained 60.47% of the variance and were sensitive to discriminate the different clinical groups, with the preoperative group having the poorest quality of life. Internal consistency ranged from 0.92 to 0.96, and concurrent validity with the ESI-55 was moderate/strong (0.32-0.70). Test-retest reliability was confirmed, with an ICC value of 0.54 (2 days), 0.91 (7 days), and 0.97 (30 days). The SHE had satisfactory psychometric qualities for use in the Brazilian population, similar to those of the original version. The instrument seems to be more adequate in psychometric terms for the postoperative and drug treatment follow-up groups, and its use should be encouraged. (c) 2012 Elsevier Inc. All rights reserved

Stir bar-sorptive extraction, solid phase extraction and liquid-liquid extraction for levetiracetam determination in human plasma: comparing recovery rates

Levetiracetam (LEV), an antiepileptic drug (AED) with favorable pharmacokinetic profile, is increasingly being used in clinical practice, although information on its metabolism and disposition are still being generated. Therefore a simple, robust and fast liquid-liquid extraction (LLE) followed by high-performance liquid chromatography method is described that could be used for both pharmacokinetic and therapeutic drug monitoring (TDM) purposes. Moreover, recovery rates of LEV in plasma were compared among LLE, stir bar-sorptive extraction (SBSE), and solid-phase extraction (SPE). Solvent extraction with dichloromethane yielded a plasma residue free from usual interferences such as commonly co-prescribed AEDs, and recoveries around 90% (LLE), 60% (SPE) and 10% (SBSE). Separation was obtained using reverse phase Select B column with ultraviolet detection (235 nm). Mobile phase consisted of methanol:sodium acetate buffer 0.125 M pH 4.4 (20:80, v/v). The method was linear over a range of 2.8-220.0 µg mL-1. The intra- and inter-assay precision and accuracy were studied at three concentrations; relative standard deviation was less than 10%. The limit of quantification was 2.8 µg mL-1. This robust method was successfully applied to analyze plasma samples from patients with epilepsy and therefore might be used for pharmacokinetic and TDM purposes.</p