title: Oral contraceptives induce lamotrigine metabolism: evidence from a double-blind, placebo-controlled trial.
abstract: OBJECTIVE
  This study evaluates the effect of oral contraceptives on lamotrigine (LTG) plasma concentrations and urine excretion of LTG metabolites in a double-blind, placebo-controlled, crossover study in patients with epilepsy.
  
  
  METHODS
  Women with epilepsy, treated with LTG in monotherapy and taking combination-type oral contraceptives, were randomized to treatment with placebo or a standard combination-type contraceptive pill. The dose-corrected trough plasma concentration of LTG and the ratio of N-2-glucuronide/unchanged LTG on urine after 21 days of concomitant placebo treatment was analyzed versus those after 21 days of concomitant treatment with the oral contraceptive pill.
  
  
  RESULTS
  The mean dose-corrected LTG concentration after placebo treatment was 84%[95% confidence interval (CI), 45-134%] higher than after oral contraceptives, signifying an almost doubling of the concentration after cessation of oral contraceptives. Most of this increase took place within the first week after oral contraceptives were stopped. The N-2-glucuronide/LTG ratio in the urine was decreased by 31% (95% CI, -20-61%) when shifting from oral contraceptives to placebo.
  
  
  CONCLUSIONS
  Cessation of oral contraceptives leads to an 84% increase in the concentration of LTG. In parallel, the excretion of the N-2-glucuronide was decreased, indicating that the changes are caused by altered LTG glucuronidation. The change in LTG concentrations was observed within 1 week of the shift of treatment, suggesting that induction and deinduction of LTG glucuronidation is faster than that seen for other metabolic pathways (e.g., cytochrome P450).
authors.affiliation: Department of Neurology, Aarhus University Hospital, Aarhus, Denmark. Jakob@farm.au.dk
authors.forename: Jakob
authors.initials: J
authors.lastname: Christensen
authors.forename: Vaiva
authors.initials: V
authors.lastname: Petrenaite
authors.forename: Jørn
authors.initials: J
authors.lastname: Atterman
authors.forename: Per
authors.initials: P
authors.lastname: Sidenius
authors.forename: Inger
authors.initials: I
authors.lastname: Ohman
authors.forename: Torbjørn
authors.initials: T
authors.lastname: Tomson
authors.forename: Anne
authors.initials: A
authors.lastname: Sabers
mesh_terms: D000328:Adult; D000927:Anticonvulsants / Q000097:blood / Q000378:metabolism* / Q000652:urine; D003277:Contraceptives, Oral, Combined / Q000493:pharmacokinetics*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004347:Drug Interactions; D004827:Epilepsy / Q000188:drug therapy* / Q000378:metabolism; D004997:Ethinyl Estradiol / Q000493:pharmacokinetics; D005260:Female; D020719:Glucuronides / Q000378:metabolism / Q000652:urine; D006801:Humans; D000077213:Lamotrigine; D010919:Placebos; D014227:Triazines / Q000097:blood / Q000378:metabolism* / Q000652:urine
chemical_list: D000927:Anticonvulsants; D003277:Contraceptives, Oral, Combined; D020719:Glucuronides; D010919:Placebos; D014227:Triazines; D004997:Ethinyl Estradiol; D000077213:Lamotrigine