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Lamotrigine and Valproate Pharmacokinetic Interactions in Epileptic Patients

Mladena Lalic1*, S. Golocorbin-Kon1, Jelena Cvejic1, Ksenija Bozic2, Hani Al-Salami3, I Mikov3 and M Mikov4
  • 1 University of Novi sad, Department of Pharmacy, Serbia
  • 2 University of Novi sad, Institute of Neurology, Serbia
  • 3 University of Otago, School of Pharmacy, New Zealand
  • 4 University of Novi sad, Department of Pharmacology, Toxicology and Clinical Pharmacology, Serbia

Introduction. Lamotrigine (LTG, 3,5-diamino-6-(2,3-dichlorphenyl)-1,2,4-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) [1-4]. 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 [5]. Results. LTG serum concentrations were increased significantly from 4.67±3.66 to 9.56±5.27 µg/ml by concomitant administration of VPA. Conclusion. 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.

References

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2. Sweetman S (2007): Martindale: The complete drug reference. London, United Kingdom.

3. Thaddeus H.G., Fiedler-Kelly J., Cox E., et al (1999): Population pharmacokinetics of lamotrigine adjunctive therapy in adults with epilepsy. J. Clin. Pharmacol., 39, 373-384.

4. Patasalos N.P., Froscher W., Pisani F., et al (2002). The importance of drug interactions in epilepsy therapy. Epilepsia, 43 (4), 365-385.

5. Patil K.M., Bodhankar S.L. (2005): Simultaneous determination of lamotrigine, phenobarbitone, carbamazepine and phenytoin in human serum by high-performance liquid chromatography. J. Pharmaceut. Biomed., 39, 181-186.

Keywords: Lamotrigine, valproate, lamotrigine-valproate interaction, Epilepsy

Conference: 8th Southeast European Congress on Xenobiotic Metabolism and Toxicity - XEMET 2010, Thessaloniki, Greece, 1 Oct - 5 Oct, 2010.

Presentation Type: Poster

Topic: Food, drugs and environmental xenobiotics

Citation: Lalic M, Golocorbin-Kon S, Cvejic J, Bozic K, Al-Salami H, Mikov I and Mikov M (2010). Lamotrigine and Valproate Pharmacokinetic Interactions in Epileptic Patients. Front. Pharmacol. Conference Abstract: 8th Southeast European Congress on Xenobiotic Metabolism and Toxicity - XEMET 2010. doi: 10.3389/conf.fphar.2010.60.00156

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Received: 05 Mar 2011; Published Online: 04 Nov 2010.

* Correspondence: Dr. Mladena Lalic, University of Novi sad, Department of Pharmacy, Novi Sad, Serbia, mladena.l@hotmail.com