ArticleClinical pharmacokinetics2018
Effect of Age-Related Factors on the Pharmacokinetics of Lamotrigine and Potential Implications for Maintenance Dose Optimisation in Future Clinical Trials.
Article in Clinical pharmacokinetics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. It is linked to 2 registered trials, which are not on this map. Cited by 21 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A Multicenter, Double-Blind, Randomized, Parallel-group Evaluation of LAMICTAL Extended-release Adjunctive Therapy in Subjects With Partial Seizures
An Open-label, Double Conversion Study to Characterize the Pharmacokinetics of Lamotrigine When Switching Patients With Epilepsy on LAMICTAL Immediate-release to Extended-release Formulation and Vice Versa
Who cites it
21 citing papers in PubMed.
- Bayesian-Based Pharmacokinetic Framework Integrated with Therapeutic Drug Monitoring for Assessing Adherence to Antiseizure Medications: A Clinical Trial Simulation Study.Journal of medical Internet research · 2026Article
- Emicizumab for preventing intracranial hemorrhage in infants with severe hemophilia A: a cost-effectiveness analysis.Blood advances · 2025Article
- Cefuroxime axetil dosing regimens and probability of target attainment in adults and children.British journal of clinical pharmacology · 2025Article
- Modeling drug retention as memory effects in obese patients using fractional and augmented models.Scientific reports · 2025Article
- Epidemiological trends and age-period-cohort effects on intracerebral hemorrhage burden across the BRICS-plus from 1992 to 2021.Frontiers in neurology · 2025Article
- Hydrotherapy and acupressure in restless legs syndrome: results of a randomized, controlled, three-armed, pilot study (HYDRAC-study).Frontiers in medicine · 2025Article
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- Genetics behind Cerebral Disease with Ocular Comorbidity: Finding Parallels between the Brain and Eye Molecular Pathology.International journal of molecular sciences · 2022Review
- The Emerging Roles of Long Non-Coding RNAs in Intellectual Disability and Related Neurodevelopmental Disorders.International journal of molecular sciences · 2022Review
- Serum copper decrease and cerebellar atrophy in patients with nitrous oxide-induced subacute combined degeneration: two cases report.BMC neurology · 2021Article
- Optical coherence tomography monitoring and diagnosing retinal changes in multiple sclerosis.Brain and behavior · 2021Review
- Diagnosis and management of migraine in ten steps.Nature reviews. Neurology · 2021Review
- Progress in the Application of Drugs for the Treatment of Multiple Sclerosis.Frontiers in pharmacology · 2021Review
- Extrapolation of Drug Clearance in Children ≤ 2 Years of Age from Empirical Models Using Data from Children (> 2 Years) and Adults.Drugs in R&D · 2020Article
- A Practical Guide to Treatment of Childhood Absence Epilepsy.Paediatric drugs · 2019Review
- The influence of concomitant antiepileptic drugs on lamotrigine serum concentrations in Northwest Chinese Han population with epilepsy.PloS one · 2019Article
- Effects of Comedication and Genetic Factors on the Population Pharmacokinetics of Lamotrigine: A Prospective Analysis in Chinese Patients With Epilepsy.Frontiers in pharmacology · 2019Article
- Comment on "Effect of Age-Related Factors on the Pharmacokinetics of Lamotrigine and Potential Implications for Maintenance Dose Optimisation in Future Clinical Trials".Clinical pharmacokinetics · 2018Article
- Authors' Reply to Standing et al.: "Effect of Age-Related Factors on the Pharmacokinetics of Lamotrigine and Potential Implications for Maintenance Dose Optimisation in Future Clinical Trials".Clinical pharmacokinetics · 2018Article
Corrections and comments
- Commented on by
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- Erratum issued
Authors and funding
5 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BACKGROUND AND
aimsIn this study, we evaluate the performance of allometric concepts to predict the implications of age and size on the pharmacokinetics of lamotrigine, and assess the dose rationale across different age groups from 0.2 to 91 years.
methodsAn allometrically scaled pharmacokinetic model was developed using adolescent and adult data, taking into account the effect of comedications. Model parameters were then used to extrapolate lamotrigine pharmacokinetics to older adults (> 65 years), children (4-12 years) and infants and toddlers (0.2-2.0 years). In addition, simulations were performed to identify the implication of different doses and dosing regimens for each population, so as to ensure steady-state concentrations within a predefined reference range.
resultsThe pharmacokinetics of lamotrigine was best described using a one-compartment model with first-order absorption and elimination. Carbamazepine, phenytoin, and valproic acid changed systemic clearance (CL) by + 76.5, + 129, and - 47.4%, respectively. Allometric principles allowed accurate extrapolation of disposition parameters to older adults and children older than 4 years of age. A maturation function was required to describe changes in exposure in younger patients. Compared with adults, a child aged 1.7 years has a 31.5% higher CL, after correcting for body weight. Patients > 65 years of age showed a decrease in CL of approximately 15%.
conclusionPopulation pharmacokinetic models are usually limited to a subgroup of patients, which may mask the identification of factors contributing to interindividual variability. The availability of an integrated model including the whole patient population provides insight into the role of age-related changes in the disposition of lamotrigine, and potential implications for maintenance dose optimisation in any future trials.
trial registrationAccording to GlaxoSmithKline's Clinical Trial Register, data from the GlaxoSmithKline studies LAM100034 and LEP103944, corresponding to ClinicalTrials.gov identifiers NCT00113165 and NCT00264615, used in this work, have been used in previous publications (doi: https://doi.org/10.1212/01.wnl.0000277698.33743.8b , https://doi.org/10.1111/j.1528-1167.2007.01274.x ).
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.