title: Factors influencing serum topiramate concentrations in routine therapeutic drug monitoring in Korean adult patients with epilepsy.
abstract: OBJECTIVE
  Topiramate (TPM) is a broad-spectrum anticonvulsant used both as an adjunctive treatment and as monotherapy. In this study, the results from a routine therapeutic drug monitoring (TDM) service for TPM are summarized. In addition, factors influencing the variability in serum concentration of TPM and the effects of comedication on serum TPM concentration were investigated.
  
  
  METHODS
  Serum measurements of TPM from a routine TDM database were analyzed retrospectively. Concentration-to-dose ratio (CDR) was calculated to assess pharmacokinetic variability. We compared CDRs for patients receiving TPM monotherapy and patients receiving TPM with other antiepileptic drugs, together with the effects of each comedication on TPM concentration were studied.
  
  
  RESULTS
  There were 510 samples from 476 adult patients. Serum TPM was below 2.0 mg/L or above 10.0 mg/L in 28.2% and 5.9% of samples, respectively. Although serum TPM was broadly related to prescribed dose, there was wide variation. Most patients using TPM were treated in combination with other anticonvulsants (90.8%). TPM-CDR in patients receiving TPM monotherapy was not significantly different from those receiving TPM in combination with nonenzyme inducers, but TPM-CDR was lower in patients who were taking inducers (P < 0.0001, Kruskal-Wallis test, Dunnett method).
  
  
  CONCLUSIONS
  A large interindividual variability in TPM serum concentrations was observed in this cohort of patients. TDM of TPM is useful in selected patients such as those suspected of poor compliance/absorption and those who may experience pharmacokinetic changes because of comedication or physiological changes.
authors.affiliation: Department of Laboratory Medicine & Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Hee Jae
authors.initials: HJ
authors.lastname: Huh
authors.forename: Eun Yeon
authors.initials: EY
authors.lastname: Joo
authors.forename: Seung Bong
authors.initials: SB
authors.lastname: Hong
authors.forename: Joong Hyun
authors.initials: JH
authors.lastname: Ahn
authors.forename: Dae-Won
authors.initials: DW
authors.lastname: Seo
authors.forename: Soo-Youn
authors.initials: SY
authors.lastname: Lee
mesh_terms: D000328:Adult; D000927:Anticonvulsants / Q000097:blood*; D016903:Drug Monitoring / Q000379:methods*; D004827:Epilepsy / Q000097:blood* / Q000188:drug therapy / Q000453:epidemiology*; D005260:Female; D005500:Follow-Up Studies; D005632:Fructose / Q000031:analogs & derivatives* / Q000097:blood; D006801:Humans; D008297:Male; D056910:Republic of Korea / Q000453:epidemiology; D012189:Retrospective Studies; D000077236:Topiramate
chemical_list: D000927:Anticonvulsants; D000077236:Topiramate; D005632:Fructose