Lamotrigine and valproate pharmacokinetics interactions in epileptic patients

Abstract

Lamotrigine (LTG, 3,5-diamino-6- (2,3-dichlorphenyl)-l,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 µg/ml by concomitant administration of VPA. Discussion: 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.