title: Impact of age, weight and concomitant treatment on lamotrigine pharmacokinetics.
abstract: OBJECTIVE
  Lamotrigine metabolism may be substantially altered with concomitant administration of valproic acid and/or carbamazepine. Such alterations may require the adjustment of lamotrigine dose to ensure optimal treatment efficacy and safety.
  
  
  METHODS
  The extent of lamotrigine interactions was investigated dependent on age, gender, weight and dose of concomitant carbamazepine and/or valproic acid in 65 patients with epilepsy. Lamotrigine plasma steady-state oral clearance (CLss/F) and area under the curve (AUCss) were calculated from the dose of drug, average steady-state concentration (Css) and interval of administration. Multiple regression analysis was used for the identification and quantification of factors that influenced lamotrigine pharmacokinetics.
  
  
  CONCLUSIONS
  Age and dose of carbamazepine and valproic acid had significant influence on lamotrigine CLss/F and AUCss. Carbamazepine was associated with a dose-dependent increase and valproic acid with a dose-dependent decrease of lamotrigine metabolism rate. The effect of carbamazepine was more pronounced. Younger patients were expected to metabolize lamotrigine more rapidly whereas overweight patients may be less susceptible to interactions. Gender had no influence on lamotrigine pharmacokinetics.
  
  
  CONCLUSIONS
  The efficacy and safety of lamotrigine may be altered by concomitant administration of carbamazepine and valproic acid. The models developed may be useful for estimating doses of lamotrigine for individual patients to minimize clinically significant interactions. Therapeutic monitoring is advisable when those drugs are used concomitantly.
authors.affiliation: Agency for Drugs and Medical Devices, Belgrade, Serbia.
authors.forename: B B
authors.initials: BB
authors.lastname: Brzaković
authors.forename: S D
authors.initials: SD
authors.lastname: Vezmar Kovačević
authors.forename: K M
authors.initials: KM
authors.lastname: Vučićević
authors.forename: B R
authors.initials: BR
authors.lastname: Miljković
authors.forename: Z J
authors.initials: ZJ
authors.lastname: Martinović
authors.forename: M V
authors.initials: MV
authors.lastname: Pokrajac
authors.forename: M Š
authors.initials: MŠ
authors.lastname: Prostran
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000927:Anticonvulsants / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology; D019540:Area Under Curve; D001835:Body Weight; D002220:Carbamazepine / Q000008:administration & dosage / Q000494:pharmacology*; D002648:Child; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004827:Epilepsy / Q000188:drug therapy; D005260:Female; D006801:Humans; D000077213:Lamotrigine; D008297:Male; D008954:Models, Biological; D012044:Regression Analysis; D012737:Sex Factors; D014227:Triazines / Q000009:adverse effects / Q000493:pharmacokinetics*; D014635:Valproic Acid / Q000008:administration & dosage / Q000494:pharmacology*; D055815:Young Adult
chemical_list: D000927:Anticonvulsants; D014227:Triazines; D002220:Carbamazepine; D014635:Valproic Acid; D000077213:Lamotrigine