Brzaković, Branka (6505872732)Branka (6505872732)BrzakovićVučićević, Katarina (6505905498)Katarina (6505905498)VučićevićKovačević, Sandra Vezmar (57204567668)Sandra Vezmar (57204567668)KovačevićMiljković, Branislava (6602266729)Branislava (6602266729)MiljkovićProstran, Milica (7004009031)Milica (7004009031)ProstranMartinović, Žarko (7003683694)Žarko (7003683694)MartinovićPokrajac, Milena (6701564186)Milena (6701564186)Pokrajac2025-06-122025-06-122014https://doi.org/10.1007/s00228-013-1606-5https://www.scopus.com/inward/record.uri?eid=2-s2.0-84895076247&doi=10.1007%2fs00228-013-1606-5&partnerID=40&md5=27c88d58e071fc97b58c201c7e7b7982https://remedy.med.bg.ac.rs/handle/123456789/8561Purpose: 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. © 2013 Springer-Verlag Berlin Heidelberg.ClearanceConcomitant medicationLamotrigineNONMEMTherapeutic drug monitoring