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Utilização terapêutica de ácido valpróico e sua quantificação em fluidos biológicos
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Abstract(s)
A epilepsia é uma patologia que afeta o sistema nervoso, caracterizada pela recorrência de crises epiléticas espontâneas (não provocadas). Esta condição condiciona diretamente a qualidade de vida do indivíduo afetado, com consequências neurobiológicas, cognitivas e sociais. Atualmente existem mais de cinquenta milhões de pessoas em todo o mundo a sofrer de epilepsia, sendo que cerca de um terço destas não demonstra uma resposta satisfatória a nenhuma das opções terapêuticas disponíveis.
O tratamento desta doença centra-se na administração de fármacos antiepiléticos, os quais devem ser escolhidos de acordo com o tipo de crise, a eficácia, efeitos adversos, tolerabilidade individual e facilidade de administração dos mesmos.
O ácido valpróico, apesar de ser um antiepilético de primeira geração, é, ainda hoje, um fármaco de eleição no tratamento de crises parciais simples ou complexas, tónico-clónicas e ataques generalizados em crianças e adultos. É também utilizado no tratamento de outras patologias do SNC, como a doença bipolar. Tal como a maioria dos antiepiléticos de primeira geração, o ácido valpróico possui uma farmacocinética complexa, com uma considerável variabilidade inter e intraindividual e uma janela terapêutica estreita. Assim, a monitorização da sua concentração, bem como dos seus metabolitos ativos, é uma prática comum para ajuste de dosagem de modo a obter uma concentração sérica dentro do intervalo desejável.
Os métodos de quantificação utilizados para a monitorização terapêutica do ácido valpróico são métodos cromatográficos ou imunoensaios. Os imunoensaios são utilizados em análises de rotina pois são técnicas rápidas e simples. As suas principais limitações são a possibilidade de ocorrência de reações cruzadas resultantes de outros compostos presentes na amostra, dando falsos resultados e a impossibilidade de detetarem mais do que um composto em simultâneo. Os métodos cromatográficos implicam um maior tempo de análise e o recurso a técnicos mais qualificados (maior custo associado) razões pelas quais não são utilizadas em análises de rotina. No entanto, são mais sensíveis, específicos e precisos, permitem a quantificação de vários compostos em simultâneo e a análise eficaz dos vários metabolitos do ácido valpróico.
Epilepsy is a pathology that affects the nervous system, characterized by the recurrence of spontaneous (unprovoked) epileptic seizures. This condition directly affects the quality of life of the affected individual, with neurobiological, cognitive and social consequences. Currently there are over fifty million people worldwide suffer from epilepsy, and about a third of these do not show a satisfactory answer to any of the treatment options available. Treatment of this disease focuses on the administration of antiepileptic drugs, which should be chosen according to the type of crisis, efficacy, adverse effects, individual tolerability and ease of administration. Valproic acid, despite being a first-generation antiepileptic, is still a drug of choice in the treatment of simple or complex partial seizures, tonic-clonic seizures and generalized seizures in children and adults. It is also used in the treatment of other CNS disorders, such as bipolar disorder. Like most first-generation antiepileptics, valproic acid has a complex pharmacokinetics with considerable inter- and intra-individual variability and a narrow therapeutic window. Thus, monitoring of its concentration as well as its active metabolites is a common practice for dosage adjustment in order to achieve a serum concentration within the desired range. The quantification methods used for the therapeutic monitoring of valproic acid are chromatographic methods or immunoassays. Immunoassays are used in routine analyzes because they are fast and simple techniques. Its main limitations are the possibility of occurrence of cross reactions resulting from the presence of other compounds in the sample, giving false results and the impossibility of detecting more than one compound at the same time. Chromatographic methods are not used in routine analyzes because they imply a longer analysis time and the presence of more qualified technicians (higher associated costs). However, they are more sensitive, specific and precise, allowing the quantification of several compounds simultaneously (valproic acid and its metabolites).
Epilepsy is a pathology that affects the nervous system, characterized by the recurrence of spontaneous (unprovoked) epileptic seizures. This condition directly affects the quality of life of the affected individual, with neurobiological, cognitive and social consequences. Currently there are over fifty million people worldwide suffer from epilepsy, and about a third of these do not show a satisfactory answer to any of the treatment options available. Treatment of this disease focuses on the administration of antiepileptic drugs, which should be chosen according to the type of crisis, efficacy, adverse effects, individual tolerability and ease of administration. Valproic acid, despite being a first-generation antiepileptic, is still a drug of choice in the treatment of simple or complex partial seizures, tonic-clonic seizures and generalized seizures in children and adults. It is also used in the treatment of other CNS disorders, such as bipolar disorder. Like most first-generation antiepileptics, valproic acid has a complex pharmacokinetics with considerable inter- and intra-individual variability and a narrow therapeutic window. Thus, monitoring of its concentration as well as its active metabolites is a common practice for dosage adjustment in order to achieve a serum concentration within the desired range. The quantification methods used for the therapeutic monitoring of valproic acid are chromatographic methods or immunoassays. Immunoassays are used in routine analyzes because they are fast and simple techniques. Its main limitations are the possibility of occurrence of cross reactions resulting from the presence of other compounds in the sample, giving false results and the impossibility of detecting more than one compound at the same time. Chromatographic methods are not used in routine analyzes because they imply a longer analysis time and the presence of more qualified technicians (higher associated costs). However, they are more sensitive, specific and precise, allowing the quantification of several compounds simultaneously (valproic acid and its metabolites).
Description
Keywords
Epilepsia Fármacos antiepiléticos Ácido valpróico Monitorização terapêutica Métodos de quantificação Imunoensaios Métodos cromatográficos Epilepsy Antiepileptic drugs Valproic acid Therapeutic monitoring Quantification methods Immunoassays Chromatographic methods