Skip to main content
SpringerLink
Log in

Lamotrigine pharmacokinetic evaluation in epileptic patients submitted to VEEG monitoring

  • Pharmacokinetics and Disposition
  • Published:
European Journal of Clinical Pharmacology Aims and scope Submit manuscript

Abstract

Objective

The aim of the present study was to evaluate the pharmacokinetic profile of lamotrigine (LTG) in epileptic patients submitted to video-electroencephalography (VEEG) monitoring and, in addition, to investigate the influence of concomitant antiepileptic drugs (AEDs) on the kinetics of LTG.

Methods

The analysis assumed a one-compartment open model with first-order absorption and elimination. The kinetic estimates obtained in this population were validated by using the Prediction-Error approach. The influence of medication was also assessed by the calculation of the LTG concentration-to-dose ratio. Patients (n=135) were divided into four groups according to the co-medication: Group 1, patients taking LTG with enzyme-inducer agents; Group 2, patients receiving LTG with valproic acid; Group 3, patients receiving both inducers and inhibitors of LTG metabolism; Group 4, patients under AEDs not known to alter LTG metabolism.

Results

The obtained estimates for clearance (CL) (L/h/kg) [0.075±0.029 (Group 1), 0.014±0.005 (Group 2), 0.025±0.008 (Group 3) and 0.044±0.011 (Group 4)] appear to be the most appropriate set to be implemented in clinical practice as prior information, as demonstrated by the accuracy and precision of the measurements. In addition, the influence of co-medication on the LTG profile was further confirmed by the basal LTG concentration-to-dose ratio.

Conclusion

The results of the present investigation may contribute to achieving the goal of optimizing patients’ clinical outcomes by managing their medication regimen through measured drug concentrations. Patients submitted to VEEG monitoring may benefit from this study, as the results may be used to provide better drug management in this medical setting.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Brodie MJ, Richens A, Yuen AWC (1995) Double-blind comparison of lamotrigine and carbamazepine in newly diagnosed epilepsy. Lancet 345:476–479

    Article  PubMed  CAS  Google Scholar 

  2. Steiner TJ, Dellaportas CI, Findley LJ, Gross M, Gibberd FB, Perkin GD, Park DM, Abbott R (1999) Lamotrigine monotherapy in newly diagnosed untreated epilepsy: a double-blind comparison with phenytoin. Epilepsia 40:601–607

    Article  PubMed  CAS  Google Scholar 

  3. Brodie MJ, Overstall PW, Giorgi L, The UK Lamotrigine Elderly Study Group (1999) Multicentre, double-blind, randomised comparison between lamotrigine and carbamazepine in elderly patients with newly diagnosed epilepsy. Epilepsy Res 37:81–87

    Article  PubMed  CAS  Google Scholar 

  4. Hurley SC (2002) Lamotrigine update and its use in mood disorders. Ann Pharmacother 36:860–873

    Article  PubMed  CAS  Google Scholar 

  5. Cohen AF, Land GS, Breimer DD, Yuen WC, Winton C, Peck AW (1987) Lamotrigine, a new anticonvulsant: pharmacokinetics in normal man. Clin Pharmacol Ther 42:535–541

    Article  PubMed  CAS  Google Scholar 

  6. Magdalou J, Herber R, Bidault R, Siest G (1992) In vitro N-glucuronidation of a novel antiepileptic drug, lamotrigine, by human liver microsomes. J Pharmacol Exp Ther 260:1166–1173

    PubMed  CAS  Google Scholar 

  7. Green MD, Bishop WP, Tephy TR (1995) Expressed human UGT1.4 protein catalyzes the formation of quaternary ammonium-linked glucuronides. Drug Metab Dispos 23:299–302

    PubMed  CAS  Google Scholar 

  8. Jawad S, Yuen WC, Peck AW, Hamilton MJ, Oxley JR, Richens A (1987) Lamotrigine: single-dose pharmacokinetics and initial 1 week experience in refractory epilepsy. Epilepsy Res 1:194–201

    Article  PubMed  CAS  Google Scholar 

  9. Yuen AWC, Land G, Weatherley BC, Peck AW (1992) Sodium valproate acutely inhibits lamotrigine metabolism. Br J Clin Pharmacol 33:511–513

    PubMed  CAS  Google Scholar 

  10. Anderson GD, Yau MK, Gidal BE, Harris SJ, Levy RH, Lai AA, Wolf KB, Wargin WA, Dren AT (1996) Bidirectional interaction of valproate and lamotrigine in healthy subjects. Clin Pharmacol Ther 60:145–156

    Article  PubMed  CAS  Google Scholar 

  11. Bottiger Y, Svensson J, Stahle L (1999) Lamotrigine drug interactions in a TDM material. Ther Drug Monit 21:171–174

    Article  PubMed  CAS  Google Scholar 

  12. Tomson T, Johannessen SI (2000) Therapeutic monitoring of the new antiepileptic drugs. Eur J Clin Pharmacol 55:697–705

    Article  PubMed  CAS  Google Scholar 

  13. Johannessen SI, Battino D, Berry Dj, Bialer M, Krämer G, Tomson T, Patsalos PN (2003) Therapeutic drug monitoring of the newer antiepileptic drugs. Ther Drug Monit 25:347–363

    Article  PubMed  CAS  Google Scholar 

  14. Castel-Branco MM, Almeida AM, Falcão AC, Macedo TA, Caramona MM, Lopez FG (2001) Lamorigine analysis in blood and brain by high-performance liquid chromatography. J Chromatogr B 755:119–127

    Article  CAS  Google Scholar 

  15. Sheiner LB, Beal SL (1981) Some suggestions for measuring predictive performance. J Pharmacokinet Biop 9:503–513

    Article  CAS  Google Scholar 

  16. May TW, Rambeck B, Jürgens U (1996) Serum concentrations of lamotrigine in epileptic patients: the influence of dose and comedication. Ther Drug Monit 18:523–531

    Article  PubMed  CAS  Google Scholar 

  17. Battino D, Croci D, Granata T, Estienne M, Pisani F, Avanzini G (1997) Lamotrigine plasma concentrations in children and adults: influence of age and associated therapy. Ther Drug Monit 19:620–627

    Article  PubMed  CAS  Google Scholar 

  18. Bartoli A, Guerrini R, Belmonte A, Alessandri MG, Gatti G, Perucca E (1997) The influence of dosage, age, and comedication on steady state plasma lamotrigine concentrations in epileptic children: a prospective study with preliminary assessment of correlations with clinical response. Ther Drug Monit 19:252–260

    Article  PubMed  CAS  Google Scholar 

  19. Armijo JA, Bravo J, Cuadrado A, Herranz JL (1999) Lamotrigine serum concentration-to-dose ratio: influence of age and concomitant antiepileptic drugs and dosage implications. Ther Drug Monit 21:182–190

    Article  PubMed  CAS  Google Scholar 

  20. Garnett WR (1997) Lamotrigine: pharmacokinetics. J Child Neurol 12:S10–S15

    Article  PubMed  Google Scholar 

  21. Grasela TH, Fiedler-Kelly J, Cox E, Womble GP, Risner ME, Chen C (1999) Population pharmacokinetics of lamotrigine adjunctive therapy in adults with epilepsy. J Clin Pharmacol 39:373–384

    Article  PubMed  CAS  Google Scholar 

  22. Chan V, Morris RG, Ilett KF, Tett SE (2001) Population Pharmacokinetics of lamotrigine. Ther Drug Monit 23:630–635

    Article  PubMed  CAS  Google Scholar 

  23. Lardizabal DV, Morris Hh, Hovinga CA, Carreño M (2003) Tolerability and pharmacokinetics of oral loading with lamotrigine in epilepsy monitoring unit. Epilepsia 44:536–539

    Article  PubMed  CAS  Google Scholar 

  24. Riva R, Albani F, Contin M, Baruzzi A (1996) Pharmacokinetic interactions between antiepileptic drugs: Clinical considerations. Clin Pharmacokinet 31:470–493

    Article  PubMed  CAS  Google Scholar 

  25. Sabers A, Buchholt JM, Uldall P, Hansen EL (2001) Lamotrigine plasma levels reduced by oral contraceptives. Epilepsy Res 47:151–154

    Article  PubMed  CAS  Google Scholar 

  26. Morris RG, Black AB, Lam E, Westley IS (2000) Clinical study of lamotrigine and valproic acid in patients with epilepsy: using a drug interaction to advantage? Ther Drug Monit 22:656–660

    Article  PubMed  CAS  Google Scholar 

  27. Gidal BE, Sheth R, Parnell J, Maloney K, Sale M (2003) Evaluation of VPA dose and concentration effects on lamotrigine pharmacokinetic: implications for conversion to lamotrigine monotherapy. Epilepsy Res 57:85–93

    Article  PubMed  CAS  Google Scholar 

  28. Benetello P, Furlanut M, Baraldo M, Tonon A, Furlanut M (2002) Therapeutic drug monitoring of lamotrigine in patients suffering from resistant partial seizures. Eur Neurol 48:200–203

    Article  PubMed  CAS  Google Scholar 

  29. Hussein Z, Posner J (1997) Population pharmacokinetics of lamotrigine monotherapy in patients with epilepsy: retrospective analysis of routine monitoring data. Br J Clin Pharmacol 43:457–465

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

We thank the Wellcome Research Laboratories for the supply of lamotrigine and the internal standard for the analytical assay (HPLC). AM Almeida was supported by Praxis XXI/BD/16288/98.

Author information

Authors and Affiliations

  1. Laboratory of Pharmacology, Faculty of Pharmacy, University of Coimbra, Largo D. Dinis, 3000-295, Coimbra, Portugal

    A. M. Almeida, A. C. Falcão, M. J. Rocha & M. M. Caramona

  2. Neurology Service, Coimbra University Hospital, 3000-075, Coimbra, Portugal

    F. Sales

  3. Laboratory of Neurochemistry, Neurology Service, Coimbra University Hospital, 3000-075, Coimbra, Portugal

    I. Baldeiras

Authors
  1. A. M. Almeida
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. A. C. Falcão
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. F. Sales
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. I. Baldeiras
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. M. J. Rocha
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. M. M. Caramona
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to A. C. Falcão.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Almeida, A.M., Falcão, A.C., Sales, F. et al. Lamotrigine pharmacokinetic evaluation in epileptic patients submitted to VEEG monitoring. Eur J Clin Pharmacol 62, 737–742 (2006). https://doi.org/10.1007/s00228-006-0144-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00228-006-0144-9

Keywords

Search

Navigation