title: Lamotrigine and valproate pharmacokinetics interactions in epileptic patients.
abstract: Lamotrigine (LTG, 3,5-diamino-6- (2,3-dichlorphenyl)-,2,4-triazine) is an antiepileptic drug used mainly for partial and generalized seizures. The efficacy of LTG in treating resistant partial seizures was optimized when it was combined with valproate (VPA). The aim of this study was to investigate the influence of VPA on LTG pharmacokinetics in epileptic patients.
  
  
  METHODS
  38 patients were randomly divided into two groups, one given LTG (n = 18) and the other given LTG + VPA(n = 20). The first group consisted of 10 females (32.50 +/- 12.46 years old, 67.80 +/- 15.18 kg) and 8 males (24.88 +/- 8.92 years old, 69.88 +/- 11.41 kg) and the second group consisted of 9 females (28.33 +/- 6.52 years old, 62.89 +/- 13.28 kg) and 11 males (37.64 +/- 10.43 years old, 85.64 +/- 15.4 kg). Patients were either administered an oral dose of LTG (157 +/- 74 mg/day) or LTG + VPA (150 +/- 83.11 mg/day & 774 +/- 330 mg/day respectively). LTG steady state serum concentrations were determined 1.5-8 h post dose. Analyses were performed by a validated HPLC method.
  
  
  RESULTS
  LTG serum concentrations were increased significantly from 4.67 +/- 3.66 and 9.56 +/- 5.27 microg/ml by concomitant administration of VPA.
  
  
  CONCLUSIONS
  The inhibition of LTG metabolism by VPA was shown to have a marked effect on LTG kinetics. This inhibitory effect was complicated further by inter-patients variation in body weight and gender. This emphasizes the importance of continuous monitoring of LTG serum concentrations on an individual basis. Accordingly, if the use of potentially interacting drugs cannot be avoided, adverse reactions can be minimized by dose adjustments guided by careful monitoring of clinical response and measurement of LTG serum concentrations.
authors: Department of Pharmacy, Faculty of Medicine, Novi Sad, Republic of Serbia. mladena.l@hotmail.com
authors: Mladena
authors: M
authors: Lalic
authors: Jelena
authors: J
authors: Cvejic
authors: Jovan
authors: J
authors: Popovic
authors: Ksenija
authors: K
authors: Bozic
authors: Svetlana
authors: S
authors: Golocorbin-Kon
authors: Hani
authors: H
authors: Al-Salami
authors: Momir
authors: M
authors: Mikov
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000927:Anticonvulsants / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology; D001835:Body Weight; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D016903:Drug Monitoring / Q000379:methods; D004827:Epilepsy / Q000188:drug therapy*; D005260:Female; D006801:Humans; D000077213:Lamotrigine; D008297:Male; D008875:Middle Aged; D012737:Sex Factors; D014227:Triazines / Q000008:administration & dosage / Q000493:pharmacokinetics*; D014635:Valproic Acid / Q000008:administration & dosage / Q000494:pharmacology*; D055815:Young Adult
chemical_list: D000927:Anticonvulsants; D014227:Triazines; D014635:Valproic Acid; D000077213:Lamotrigine