Ilona Burianová1, Klára Bořecká2. 1. Department of Clinical Biochemistry, Thomayer Hospital, Prague, Czech Republic; Department of Biochemistry, Faculty of Science, Charles University, Prague, Czech Republic. 2. Department of Clinical Biochemistry, Thomayer Hospital, Prague, Czech Republic. Electronic address: klara.borecka@ftn.cz.
Abstract
OBJECTIVES: Carbamazepine (CBZ) is primarily used in the treatment of epilepsy as well as trigeminal neuralgia. It is metabolised by the liver to its pharmacologically active metabolite carbamazepine-10,11-epoxide (CBZ-E), which is potentially toxic. The aim of our study was to measure CBZ and CBZ-E in our patient set and to consider the introduction of CBZ-E to routine therapeutic drug monitoring (TDM). High-performance liquid chromatography (HPLC) and Chemiluminescence Microparticle Immuno Assay (CMIA) methods for the measurement of CBZ were compared. DESIGN AND METHODS: We simultaneously measured serum concentrations of CBZ and CBZ-E using HPLC. Serum concentrations of CBZ were also analysed by CMIA. For the measurements we chose patients (ages 5-67years) on monotherapy (n=51), patients taking CBZ with antiepileptic drugs (AEDs) susceptible to pharmacokinetic interaction including phenytoin, phenobarbital, primidone and valproic acid (n=56) and patients taking other AEDs (n=44). RESULTS: Patient's serum levels of CBZ-E ranged from 1.38-27.79μmol/L with a mean value of 6.96±4.07μmol/L. The CBZ-E/CBZ ratio increased significantly in patients taking phenytoin, phenobarbital, primidone and valproic acid. CBZ concentrations measured by CMIA were lower than those obtained by HPLC (mean difference of 3.8μmol/L). The Passing and Bablok regression showed acceptable agreement between these two methods. CONCLUSIONS: Based on our results, we do not consider the introduction of the active metabolite of CBZ to routine TDM to be necessary. However, it might be beneficial in patients taking CBZ with AEDs susceptible to pharmacokinetic interaction to avoid any potential adverse effects. A close correlation between CMIA and HPLC method was found for the measurement of CBZ serum concentrations.
OBJECTIVES:Carbamazepine (CBZ) is primarily used in the treatment of epilepsy as well as trigeminal neuralgia. It is metabolised by the liver to its pharmacologically active metabolite carbamazepine-10,11-epoxide (CBZ-E), which is potentially toxic. The aim of our study was to measure CBZ and CBZ-E in our patient set and to consider the introduction of CBZ-E to routine therapeutic drug monitoring (TDM). High-performance liquid chromatography (HPLC) and Chemiluminescence Microparticle Immuno Assay (CMIA) methods for the measurement of CBZ were compared. DESIGN AND METHODS: We simultaneously measured serum concentrations of CBZ and CBZ-E using HPLC. Serum concentrations of CBZ were also analysed by CMIA. For the measurements we chose patients (ages 5-67years) on monotherapy (n=51), patients taking CBZ with antiepileptic drugs (AEDs) susceptible to pharmacokinetic interaction including phenytoin, phenobarbital, primidone and valproic acid (n=56) and patients taking other AEDs (n=44). RESULTS:Patient's serum levels of CBZ-E ranged from 1.38-27.79μmol/L with a mean value of 6.96±4.07μmol/L. The CBZ-E/CBZ ratio increased significantly in patients taking phenytoin, phenobarbital, primidone and valproic acid. CBZ concentrations measured by CMIA were lower than those obtained by HPLC (mean difference of 3.8μmol/L). The Passing and Bablok regression showed acceptable agreement between these two methods. CONCLUSIONS: Based on our results, we do not consider the introduction of the active metabolite of CBZ to routine TDM to be necessary. However, it might be beneficial in patients taking CBZ with AEDs susceptible to pharmacokinetic interaction to avoid any potential adverse effects. A close correlation between CMIA and HPLC method was found for the measurement of CBZ serum concentrations.