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Pharmacokinetics of lamotrigine in paediatric and young adult epileptic patients—nonlinear mixed effects modelling approach

  • Pharmacokinetics and Disposition
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Abstract

Purpose

The purpose of the study was to examine and describe adjunctive lamotrigine (LTG) pharmacokinetics in paediatric and young adult patients using a nonlinear mixed effects modelling (NONMEM) approach.

Methods

The study included 53 patients (age range 3–35 years) who were concomitantly treated with carbamazepine (CBZ) and/or valproic acid (VPA). A total of 70 blood samples corresponding to trough levels were available for analysis. Data were modelled, and the final model was evaluated using NONMEM and auxiliary software tools.

Results

The final LTG population model included the effects of concomitant drugs and patient’s weight (WT) which stratified the population into three groups: ≤25 kg, >25 to <60 kg and ≥60 kg. Based on the final model, the estimated LTG oral clearance (CL/F) for a typical patient weighing ≤25 kg, >25 to <60 kg or ≥60 kg who was concomitantly treated with CBZ was estimated to be 3.28, 4.23, or 7.15 l/h, respectively. If a patient was concomitantly treated with CBZ + VPA, the CL/F decreased on average by 69.5 % relative to LTG + CBZ co-therapy. VPA was found to decrease the LTG CL/F by 87.6 % compared to co-therapy with only CBZ.

Conclusion

The LTG population pharmacokinetic model developed in this study may be a reliable method for individualising the LTG dosing regimen in paediatric and young adult patients on combination therapy during therapeutic drug monitoring.

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Acknowledgements

This work was conducted as a part of the project Experimental and Clinical Pharmacological Investigations of Mechanisms of Drug Action and Interactions in Nervous and Cardiovascular System (No. 175023) funded by Ministry of Education, Science and Technological Development, Belgrade, Republic of Serbia.

We are very grateful to the personnel from the Institute of Mental Health, Belgrade. Additionally, the authors would like to acknowledge our colleague at Spec. Clin. Pharm., Ružica Veličković, for her significant contribution to the research.

Conflict of Interest

None.

Author information

Authors and Affiliations

  1. Medicines and Medical Devices Agency of Serbia, Belgrade, Serbia

    Branka Brzaković

  2. Department of Pharmacokinetics and Clinical Pharmacy, University of Belgrade - Faculty of Pharmacy, Vojvode Stepe 450, 11000, Belgrade, Serbia

    Katarina Vučićević, Sandra Vezmar Kovačević, Branislava Miljković & Milena Pokrajac

  3. Department of Pharmacology, Clinical Pharmacology and Toxicology, University of Belgrade - School of Medicine, Belgrade, Serbia

    Milica Prostran

  4. Institute of Mental Health, Department of Epilepsy and Clinical Neurophysiology, University of Belgrade - School of Medicine, Belgrade, Serbia

    Žarko Martinović

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  1. Branka Brzaković
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Correspondence to Katarina Vučićević.

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Brzaković, B., Vučićević, K., Kovačević, S.V. et al. Pharmacokinetics of lamotrigine in paediatric and young adult epileptic patients—nonlinear mixed effects modelling approach. Eur J Clin Pharmacol 70, 179–185 (2014). https://doi.org/10.1007/s00228-013-1606-5

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  • DOI: https://doi.org/10.1007/s00228-013-1606-5

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