title: Influence of carbamazepine-10,11-epoxide on the serum level of valproic acid in epileptic patients on combined treatment with carbamazepine and valproic acid.
abstract: BACKGROUND
  Possible drug interactions in comedication have been the focus of intensive studies in the last decade. Polytherapy is often resorted to in epilepsy, and then the effect of factors such as gender, age, and metabolism should be taken into consideration. In this country, the anticonvulsant drugs used very frequently in a combined treatment of epilepsy are carbamazepine (CBZ) and valproic acid (VPA). The effect of CBZ is determined by the presence of its active metabolite carbamazepine-10.11-epoxide (CBZ-E) in blood serum.
  
  
  OBJECTIVE
  The purpose of the study was to find whether CBZ-E has any effect on the VPA serum level and whether this effect is age-dependent.
  
  
  METHODS
  Blood samples from 52 epileptic patients on comedication with CBZ and VPA aged 3 to 53 years were examined. The patients were allocated into four age groups: preschool age (from 3 to 6 years)--9 patients; school age (from 7 to 14 years)--8 patients; adolescence (from 15 to 18 years)--11 patients, and adults (from 19 to 53 years)--24 patients. The serum levels of CBZ, CBZ-E, VPA were determined by gas chromatography. The ratio CBZ-E/CBZ of every patient was calculated.
  
  
  RESULTS
  The CBZ and VPA levels we found were within the limits of their respective therapeutic ranges. The mean values of the serum level of the two drugs showed no statistically significant difference in the four age groups. In the school age group the mean values of CBZ and VPA were the lowest compared to the other age groups.
  
  
  CONCLUSIONS
  The effect of CBZ-E serum level upon VPA serum level is age-dependent. In preschool age VPA manifests itself as inhibitor of CBZ-E metabolism. The ratio CBZ-E/CBZ does not affect the VPA serum level in combined therapy with these two drugs.
authors.affiliation: Higher Medical Institute, Department of Pharmacology and Drug Toxicology, 15A Vassil Aprilov St., 4000 Plovdiv, Bulgaria.
authors.forename: G D
authors.initials: GD
authors.lastname: Minkova
authors.forename: D P
authors.initials: DP
authors.lastname: Getova
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000927:Anticonvulsants / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002220:Carbamazepine / Q000031:analogs & derivatives* / Q000097:blood* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D004827:Epilepsy / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D008875:Middle Aged; D014635:Valproic Acid / Q000493:pharmacokinetics / Q000627:therapeutic use*
chemical_list: D000927:Anticonvulsants; D002220:Carbamazepine; D014635:Valproic Acid; C012227:carbamazepine epoxide