ArticleEuropean journal of clinical pharmacology2018
Population pharmacokinetics of lamotrigine co-administered with valproic acid in Chinese epileptic children using nonlinear mixed effects modeling.
Article in European journal of clinical pharmacology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed, 22 citations in OpenAlex.
- A comparative study on the efficacy of different combinational anti-seizure medication therapies following valproate monotherapy failure.Acta epileptologica · 2025Article
- Association of SCN1A Gene Polymorphisms with Sodium Valproate Resistance in Pediatric Epilepsy: A Retrospective Case-Control Study.Neuropsychiatric disease and treatment · 2025Article
- Influencing risk factors of voriconazole-induced liver injury in Uygur pediatric patients undergoing allogeneic hematopoietic stem cell transplantation.BMC pediatrics · 2024Article
- Joint use of population pharmacokinetics and machine learning for optimizing antiepileptic treatment in pediatric population.Therapeutic advances in drug safety · 2023Article
- A machine learning approach to personalized dose adjustment of lamotrigine using noninvasive clinical parameters.Scientific reports · 2021Article
- Variation in 100 relevant pharmacogenes among emiratis with insights from understudied populations.Scientific reports · 2020Article
- Impact of gender, albumin, and CYP2C19 polymorphisms on valproic acid in Chinese patients: a population pharmacokinetic model.The Journal of international medical research · 2020Article
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
purposeThe aims of this study were to develop a population pharmacokinetic (PPK) model of lamotrigine (LTG) in Chinese epileptic children by using nonlinear mixed effects modeling (NONMEM) and to investigate the effects of valproic acid (VPA) and genetic polymorphisms of the major metabolizing enzymes (UGT1A4, UGT2B7) on the pharmacokinetics of LTG.
methodsA total of 182 epileptic children who were treated with LTG as monotherapy or as part of combination therapy were included in this study as the model group, and 61 patients were included as the validation group. The steady-state serum trough concentrations of LTG and VPA were determined using a high-performance liquid chromatography method and fluorescence polarization immunoassay, respectively. Patients were genotyped for three single nucleotide polymorphisms (UGT1A4 142T>G, UGT2B7 -161C>T, and UGT2B7 802C>T). PPK analysis was performed with NONMEM using first-order absorption and elimination. Bootstrap, normalized prediction distribution errors and external evaluations were performed to determine the stability and predictive performance of the model.
resultsFor the final model, the oral clearance (CL/F) of LTG was estimated to be 0.705 L/h with inter-individual variability (IIV) of 21.3%. The estimates generated by NONMEM indicated that the LTG CL/F was significantly influenced by patient body weight (increased with an exponent of 0.574) and VPA concentration (decreased with linearity of 0.273 with co-administration). However, no significant effects of UGT1A4 or UGT2B7 polymorphisms on LTG CL/F were noted in this population of Chinese children.
conclusionThis study confirms the interaction of LTG with VPA, which likely depends on VPA concentration. The LTG PPK model developed in this study could be useful for individualizing LTG dosage regimens in pediatric patients receiving combination therapy, especially therapy that includes VPA.
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