title: Drug interaction and pharmacokinetic modeling of oxcarbazepine in korean patients with epilepsy.
abstract: OBJECTIVE
  To determine first whether there was a clear relationship between concentrations of the active metabolite of oxcarbazepine (OXC), 10-hydroxycarbamazepine (OHC), and dose adjusted for weight, and second, whether the clearance of OHC was influenced by comedication with enzyme-inducing antiepileptic drugs (EIAED).
  
  
  METHODS
  We analyzed 254 cases (patients 3-80 years of age) of OXC therapeutic drug monitoring, retrospectively. The cases were categorized into OXC monotherapy (n = 78), OXC in combination with EIAED (n = 73), and OXC in combination with non-EIAED (n = 103). The serum OHC concentrations of predose samples were measured by high-performance liquid chromatography. A population pharmacokinetic model was developed using NONMEM.
  
  
  RESULTS
  The mean ± SD serum concentration of OHC was 14.47 ± 8.28 μg/mL at a mean daily dose of 16.22 ± 7.99 mg/kg. The serum concentration of OHC was correlated with the OXC dose per body weight (r = 0.6005; P < 0.0001). No association was found between OHC concentration and patient age, weight, sex, or seizure type. The concentration-to-dose ratio on OXC in combination with EIAED was significantly lower than that on OXC monotherapy (P = 0.002) or OXC in combination with non-EIAED (P < 0.0001). In population pharmacokinetic modeling, the apparent clearance of OHC was higher by 31.2% in combination with EIAED than in other groups.
  
  
  CONCLUSIONS
  The serum concentration of OHC was statistically significantly correlated with the dose of OXC and negatively correlated with comedication of EIAED. Population pharmacokinetic analysis showed that the apparent clearance of OHC increased with comedication with EIAEDs.
authors.affiliation: Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Kyoung-Jin
authors.initials: KJ
authors.lastname: Park
authors.forename: Jung-Ryul
authors.initials: JR
authors.lastname: Kim
authors.forename: Eun Yeon
authors.initials: EY
authors.lastname: Joo
authors.forename: Dae Won
authors.initials: DW
authors.lastname: Seo
authors.forename: Seung Bong
authors.initials: SB
authors.lastname: Hong
authors.forename: Jae-Wook
authors.initials: JW
authors.lastname: Ko
authors.forename: Suk-Ran
authors.initials: SR
authors.lastname: Kim
authors.forename: Wooseong
authors.initials: W
authors.lastname: Huh
authors.forename: Soo-Youn
authors.initials: SY
authors.lastname: Lee
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000927:Anticonvulsants / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*; D002220:Carbamazepine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000097:blood / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D002851:Chromatography, High Pressure Liquid; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D016903:Drug Monitoring; D004359:Drug Therapy, Combination; D004827:Epilepsy / Q000188:drug therapy*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D000078330:Oxcarbazepine; D010634:Phenobarbital / Q000097:blood / Q000627:therapeutic use; D010672:Phenytoin / Q000097:blood / Q000627:therapeutic use; D056910:Republic of Korea; D012189:Retrospective Studies; D055815:Young Adult
chemical_list: C039775:10,11-dihydro-10-hydroxycarbamazepine; D000927:Anticonvulsants; D002220:Carbamazepine; D010672:Phenytoin; D000078330:Oxcarbazepine; D010634:Phenobarbital