Pharmacokinetics of lamotrigine in paediatric and young adult epileptic patients—nonlinear mixed effects modelling approach
In: European journal of clinical pharmacology, Jg. 70 (2014), Heft 2, S. 179-185
Online
academicJournal
- print, 44 ref
Zugriff:
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 1/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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Pharmacokinetics of lamotrigine in paediatric and young adult epileptic patients—nonlinear mixed effects modelling approach
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Autor/in / Beteiligte Person: | BRZAKOVIC, Branka ; VUCICEVIC, Katarina ; KOVACEVIC, Sandra Vezmar ; MILJKOVIC, Branislava ; PROSTRAN, Milica ; MARTINOVIC, Zarko ; POKRAJAC, Milena |
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Zeitschrift: | European journal of clinical pharmacology, Jg. 70 (2014), Heft 2, S. 179-185 |
Veröffentlichung: | Heidelberg: Springer, 2014 |
Medientyp: | academicJournal |
Umfang: | print, 44 ref |
ISSN: | 0031-6970 (print) |
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