title: Routine therapeutic monitoring of the active metabolite of carbamazepine: Is it really necessary?
abstract: OBJECTIVE
  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.
  
  
  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.
authors.affiliation: Department of Clinical Biochemistry, Thomayer Hospital, Prague, Czech Republic; Department of Biochemistry, Faculty of Science, Charles University, Prague, Czech Republic.
authors.forename: Ilona
authors.initials: I
authors.lastname: Burianová
authors.affiliation: Department of Clinical Biochemistry, Thomayer Hospital, Prague, Czech Republic. Electronic address: klara.borecka@ftn.cz.
authors.forename: Klára
authors.initials: K
authors.lastname: Bořecká
mesh_terms: D002220:Carbamazepine / Q000031:analogs & derivatives* / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D016903:Drug Monitoring; D004359:Drug Therapy, Combination; D006801:Humans; D007118:Immunoassay; D012044:Regression Analysis
chemical_list: D002220:Carbamazepine; C012227:carbamazepine epoxide
keywords: Antiepileptic drugs; Carbamazepine; Carbamazepine-10,11-epoxide; High-performance liquid chromatography; Immunoassay; Therapeutic drug monitoring