Dosing Recommendations for Lamotrigine in Children: Evaluation Based on Previous and New Population Pharmacokinetic Models
| Autor: | Radia Aboura, Naïm Bouazza, Inès Gana, Jean-Marc Tréluyer, Isabelle Desguerre, Camille Chenevier-Gobeaux, Yi Zheng, Rima Nabbout, Déborah Hirt, Manon Tauzin, Sihem Benaboud, Cécile Freihuber, Thierry Billette de Villemeur |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Male
Pediatrics medicine.medical_specialty Adolescent Metabolic Clearance Rate Population Lamotrigine Models Biological 030226 pharmacology & pharmacy 03 medical and health sciences 0302 clinical medicine Pharmacokinetics medicine Humans Pharmacology (medical) Dosing Child education Pharmacology education.field_of_study Epilepsy Dose-Response Relationship Drug medicine.diagnostic_test business.industry Body Weight Infant New population Therapeutic drug monitoring Child Preschool 030220 oncology & carcinogenesis Cohort Anticonvulsants Female Drug Monitoring business medicine.drug Pediatric population |
| Zdroj: | The Journal of Clinical Pharmacology. 61:677-687 |
| ISSN: | 1552-4604 0091-2700 |
| Popis: | Lamotrigine is a broad-spectrum antiepileptic drug with high interindividual variability in serum concentrations in children. The aims of this study were to evaluate the predictive performance of pediatric population pharmacokinetic (PPK) models published on lamotrigine, to build a new model with our monitoring data and to evaluate the current recommended doses. A validation cohort included patients treated with lamotrigine who had a serum level assayed during therapeutic drug monitoring (TDM). PPK models published in the literature were first applied to the validation cohort. We assessed their predictive performance using mean prediction errors, root mean squared errors, and visual predictive checks. A new model was then built using the data. Dose simulations were performed to evaluate the doses recommended. We included 270 lamotrigine concentrations ranging from 0.5 to 17.9 mg/L from 175 patients. The median (range) age and weight were 11.8 years (0.8-18 years) and 32.7 kg (8-110 kg). We tested 6 PPK models; most had acceptable bias and precision but underestimated the variability of the cohort. We built a 1-compartment model with first-order absorption and elimination, allometric scaling, and effects of inhibitor and inducer comedications. In our cohort, 22.6% of trough concentrations were below 2.5 mg/L. In conclusion, we proposed a PPK model that can be used for TDM of lamotrigine in children. In our population, a high percentage of children had low trough concentrations of lamotrigine. As the intervals of recommended doses are large, we suggest aiming at the higher range of doses to reach the target concentration. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Plný text