中国药房2025，Vol.36Issue(5)：594-599,6.DOI:10.6039/j.issn.1001-0408.2025.05.16
左乙拉西坦在脑卒中后癫痫患者中的群体药动学研究
Study on population pharmacokinetics of levetiracetam in post-stroke epilepsy patients
摘要
Abstract
OBJECTIVE To establish population pharmacokinetic model of levetiracetam(Lev)for Chinese patients with post-stroke epilepsy(PSE),and provide reference for formulating individualized dosing regimens for Lev therapy in this specific population.METHODS Blood concentration data and clinical diagnosis and treatment information of PSE patients meeting the inclusion criteria were retrospectively collected and divided into model group and validation group at an 8:2 ratio using a random number method.Based on the model group data,a population pharmacokinetic model was developed using nonlinear mixed-effects modeling.Internal evaluation was performed through goodness-of-fit tests and bootstrap analysis,while external validation was conducted using the validation group data.RESULTS A total of 75 blood concentration measurements from 70 PSE patients were collected,with 60 measurements from 55 patients used for model development and 15 measurements from 15 patients reserved for external validation.The final model estimated a population typical value of clearance at 2.98 L/h.Estimated glomerular filtration rate,daily dose,and homocysteine level significantly influenced clearance of Lev(P＜0.01).The model demonstrated satisfactory predictive performance,as evidenced by goodness-of-fit tests,bootstrap analysis,and external validation results.CONCLUSIONS Daily dose,estimated glomerular filtration rate,and homocysteine level are identified as significant covariates influencing Lev clearance in Chinese PSE patients.When making clinical decisions,comprehensive consideration should be given to the patient's treatment response,physiological and pathological conditions,and the occurrence of adverse reactions,etc.The dosage of Lev should be adjusted based on the results of population pharmacokinetic model.关键词
左乙拉西坦/脑卒中后癫痫/群体药动学/个体化用药/清除率Key words
levetiracetam/post-stroke epilepsy/population pharmacokinetics/individualized medication/clearance分类
药学引用本文复制引用
刘晨茜,吴茵,贾彩云,崔赛,吴惠珍,王素星..左乙拉西坦在脑卒中后癫痫患者中的群体药动学研究[J].中国药房,2025,36(5):594-599,6.基金项目
河北省自然科学基金项目(No.H2019307100) （No.H2019307100）
河北省医学适用技术跟踪项目(No.gz2024013) （No.gz2024013）
