Pharmacokinetics of lamotrigine in paediatric and young adult epileptic patients-nonlinear mixed effects modelling approach
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2014
Authors
Brzaković, BrankaVučićević, Katarina

Vezmar-Kovačević, Sandra

Miljković, Branislava

Prostran, Milica

Martinović, Žarko J.
Pokrajac, Milena
Article (Published version)

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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. 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. The final LTG population model included the effects of concomitant drugs and patient's weight (WT) which stratified the population into three groups: a parts per thousand currency sign25 kg, > 25 to lt 60 kg and a parts per thousand yen60 kg. Based on the final model, the estimated LTG oral clearance (CL/F) for a typical patient weighing a parts per thousand currency sign25 kg, > 25 to lt 60 kg or a parts per thousand yen60 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. 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.
Keywords:
Lamotrigine / Therapeutic drug monitoring / Concomitant medication / Clearance / NONMEMSource:
European Journal of Clinical Pharmacology, 2014, 70, 2, 179-185Publisher:
- Springer Heidelberg, Heidelberg
Funding / projects:
DOI: 10.1007/s00228-013-1606-5
ISSN: 0031-6970
PubMed: 24240511
WoS: 000330035900007
Scopus: 2-s2.0-84895076247
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PharmacyTY - JOUR AU - Brzaković, Branka AU - Vučićević, Katarina AU - Vezmar-Kovačević, Sandra AU - Miljković, Branislava AU - Prostran, Milica AU - Martinović, Žarko J. AU - Pokrajac, Milena PY - 2014 UR - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2183 AB - 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. 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. The final LTG population model included the effects of concomitant drugs and patient's weight (WT) which stratified the population into three groups: a parts per thousand currency sign25 kg, > 25 to lt 60 kg and a parts per thousand yen60 kg. Based on the final model, the estimated LTG oral clearance (CL/F) for a typical patient weighing a parts per thousand currency sign25 kg, > 25 to lt 60 kg or a parts per thousand yen60 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. 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. PB - Springer Heidelberg, Heidelberg T2 - European Journal of Clinical Pharmacology T1 - Pharmacokinetics of lamotrigine in paediatric and young adult epileptic patients-nonlinear mixed effects modelling approach VL - 70 IS - 2 SP - 179 EP - 185 DO - 10.1007/s00228-013-1606-5 ER -
@article{ author = "Brzaković, Branka and Vučićević, Katarina and Vezmar-Kovačević, Sandra and Miljković, Branislava and Prostran, Milica and Martinović, Žarko J. and Pokrajac, Milena", year = "2014", abstract = "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. 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. The final LTG population model included the effects of concomitant drugs and patient's weight (WT) which stratified the population into three groups: a parts per thousand currency sign25 kg, > 25 to lt 60 kg and a parts per thousand yen60 kg. Based on the final model, the estimated LTG oral clearance (CL/F) for a typical patient weighing a parts per thousand currency sign25 kg, > 25 to lt 60 kg or a parts per thousand yen60 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. 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.", publisher = "Springer Heidelberg, Heidelberg", journal = "European Journal of Clinical Pharmacology", title = "Pharmacokinetics of lamotrigine in paediatric and young adult epileptic patients-nonlinear mixed effects modelling approach", volume = "70", number = "2", pages = "179-185", doi = "10.1007/s00228-013-1606-5" }
Brzaković, B., Vučićević, K., Vezmar-Kovačević, S., Miljković, B., Prostran, M., Martinović, Ž. J.,& Pokrajac, M.. (2014). Pharmacokinetics of lamotrigine in paediatric and young adult epileptic patients-nonlinear mixed effects modelling approach. in European Journal of Clinical Pharmacology Springer Heidelberg, Heidelberg., 70(2), 179-185. https://doi.org/10.1007/s00228-013-1606-5
Brzaković B, Vučićević K, Vezmar-Kovačević S, Miljković B, Prostran M, Martinović ŽJ, Pokrajac M. Pharmacokinetics of lamotrigine in paediatric and young adult epileptic patients-nonlinear mixed effects modelling approach. in European Journal of Clinical Pharmacology. 2014;70(2):179-185. doi:10.1007/s00228-013-1606-5 .
Brzaković, Branka, Vučićević, Katarina, Vezmar-Kovačević, Sandra, Miljković, Branislava, Prostran, Milica, Martinović, Žarko J., Pokrajac, Milena, "Pharmacokinetics of lamotrigine in paediatric and young adult epileptic patients-nonlinear mixed effects modelling approach" in European Journal of Clinical Pharmacology, 70, no. 2 (2014):179-185, https://doi.org/10.1007/s00228-013-1606-5 . .