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

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 treate...

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Publicado en:European Journal of Clinical Pharmacology Vol. 70; no. 2; pp. 179 - 186
Autores principales: Brzaković, Branka, Vučićević, Katarina, Kovačević, Sandra, Miljković, Branislava, Prostran, Milica, Martinović, Žarko, Pokrajac, Milena
Formato: research tables/charts Journal Article
Publicado: Springer Nature Feb2014
Acceso en línea:Ver este registro en EBSCOhost
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      dt: Feb2014
      vid: 70
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      pub: Springer Nature
      place: New York, New York
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        10.1007/s00228-013-1606-5
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        atl: Pharmacokinetics of lamotrigine in paediatric and young adult epileptic patients-nonlinear mixed effects modelling approach.
      aug:
        au:
          Brzaković, Branka
          Vučićević, Katarina
          Kovačević, Sandra
          Miljković, Branislava
          Prostran, Milica
          Martinović, Žarko
          Pokrajac, Milena
        affil: Medicines and Medical Devices Agency of Serbia, Belgrade Serbia
      sug:
        subj:
          Lamotrigine Pharmacokinetics
          Epilepsy Drug Therapy
          Models, Statistical
          Lamotrigine Administration and Dosage
          Human
          Child, Preschool
          Child
          Adolescence
          Adult
          Carbamazepine Administration and Dosage
          Valproic Acid Administration and Dosage
          Descriptive Statistics
          Prospective Studies
          Serbia
          Data Analysis Software
          Maximum Likelihood
          Chi Square Test
          Male
          Female
          Confidence Intervals
          Funding Source
          Child, Preschool: 2-5 years
          Child: 6-12 years
          Adolescent: 13-18 years
          Adult: 19-44 years
          Male
          Female
      ab: 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.
      pubtype: Academic Journal
      doctype:
        research
        tables/charts
        Journal Article
      ougenre: Article
    language: English
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