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...
| Publicado en: | European Journal of Clinical Pharmacology Vol. 70; no. 2; pp. 179 - 186 |
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| Autores principales: | , , , , , , |
| Formato: | research tables/charts Journal Article |
| Publicado: |
Springer Nature
Feb2014
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=104006864&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 104006864 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 00316970 NP9 jtl: European Journal of Clinical Pharmacology issn: 00316970 maglogo: N pubinfo: dt: Feb2014 vid: 70 iid: 2 pid: 237 pub: Springer Nature place: New York, New York artinfo: ui: 104006864 93707002 10.1007/s00228-013-1606-5 NLM24240511 104006864 ppf: 179 ppct: 7 formats: fmt: @attributes: type: P tig: 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 refInfo: holdings: @attributes: islocal: N |
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