ABSTRACT
Therapeutic drug monitoring (TDM) of carbamazepine (CBZ) in saliva is an attractive alternative, because its collection is painless, non-invasive and simpler than drawing blood. Salivary drug levels, also closely reflect the free drug concentration. The aim of the study was to evaluate the suitability of saliva in routine TDM of CBZ in adult epileptic patients. Blood and saliva samples were taken simultaneously at 0 hours and 24 hours of CBZ dosing from 31 epileptic patients, receiving CBZ monotherapy for three or more months. Levels of CBZ in both these fluids were measured by high performance liquid chromatography. Strong and highly significant correlation was found between serum and salivary CBZ concentration (r = 0.659, p<0.001). Estimation of CBZ level in saliva is thus a practicable, valid and convenient method of TDM in epileptic patients.
Subject(s)
Adolescent , Adult , Anticonvulsants/metabolism , Blood/metabolism , Carbamazepine/metabolism , Drug Monitoring , Epilepsy/drug therapy , Humans , Middle Aged , Osmolar Concentration , Saliva/metabolismABSTRACT
The bioavailability of carba,azepine from 4 comercially available products was evaluated in 12 healthy volonteers. A crossover design was used and each patients received 400 mg of each product. Plasma levels of the drug were determined periodically for 72 h using a gas-liquid chromatographic method. An open model of one compartment for first-order absortion was assumed to derive pharmacokinetic parameters. Dissolution kinetics was also evaluated in each product. Significant differences in biovailability were shown for one product. Results correlated with the in vitro dissolution findings
Subject(s)
Adult , Humans , Male , Carbamazepine/pharmacology , Carbamazepine/metabolism , Biological AvailabilityABSTRACT
The percentage protein binding of antiepileptic drugs was investigated in epileptic patients (n = 90) undergoing treatment with phenobarbitone, phenytoin and carbamazepine either as a single drug therapy or in different combinations. When administered individually, the percentage (mean +/- SEM) protein binding of phenobarbitone, phenytoin and carbamazepine were 50.84 +/- 7.03, 87.23 +/- 2.98 and 76.80 +/- 6.30 respectively. Combination of phenobarbitone and phenytoin resulted in percentage (mean +/- SEM) protein binding of 51.94 +/- 6.09 for phenobarbitone and 83.54 +/- 7.01 for phenytoin, while the combination of phenobarbitone and carbamazepine resulted in percentage (mean +/- SEM) protein binding of 49.60 +/- 2.59 for phenobarbitone and 79.10 +/- 3.31 for carbamazepine. When phenytoin was given with carbamazepine percentage (mean +/- SEM) protein binding was 87.22 +/- 4.48 for phenytoin and 72.50 +/- 5.92 for carbamazepine.
Subject(s)
Adolescent , Adult , Anticonvulsants/administration & dosage , Blood Proteins/drug effects , Carbamazepine/metabolism , Drug Therapy, Combination , Epilepsy/drug therapy , Female , Humans , Male , Middle Aged , Phenobarbital/metabolism , Phenytoin/metabolism , Protein Binding , Sri LankaABSTRACT
O uso de carbamazepina no tratamento de doenças psiquiátricas é revisto. O mecanismo de açäo da carbamazepina pode ser relacionado a inibiçäo do Kindling (estimulaçäo elétrica subterapêutica repetida) no lobo temporal e no sistema límbico. Em muitos estudos já publicados, a carbamazepina foi útil no tratamento de distúrbios afetivos, especialmente em pacientes com distúrbios maníacos bipolares. Em estudos controlados, duplo-cegos, em pacientes com doenças afetivas primárias esquizoafetivas, a carbamazepina diminuiu significativamente os sintomas maníacos e mostrou efeito antidepressivo. Efeito sinergético foi observado quando a carbamazepina foi associada ao lítio. A carbamazepina também diminui sintomas em pacientes com agressäo, síndromes de descontrole, esquizofrenia e síndrome de síndrome de álcool, porém apenas poucos estudos foram controlados e comparativos; a carbamazepina pode ser útil em pacientes com aqueles distúrbios que näo respondam a terapias convencionais. Efeitos benéficos da carbamazepina em distúrbios psiquiátricos säo geralmente observados com doses de 400 a 1600 mg/dia e concentraçöes plasmáticas de 8-12 microng/ml. carbamazepina é útil em monoterapia ou combinada com outros agentes para distúrbios afetivos bipolares, especialmente em pacientes intolerantes ou que näo respondam ao lítio. Concentraçäo plasmática de carbamazepina, perfil hematológico e eletrólitos séricos devem ser monitorados cuidadosamente a fim de minimizar o risco de toxicidade