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学科主题: 临床医学
题名:
Population pharmacokinetics of lamotrigine in Chinese children with epilepsy
作者: He, Da-ke1,2; Wang, Li1; Lu, Wei3; Qin, Jiong1; Zhang, Shen4; Li, Ling2; Zhang, Jian-ming2; Bao, Wei-qun2; Song, Xiao-qing2; Liu, Hai-tao5
关键词: lamotrigine ; Chinese children ; population pharmacokinetics ; NONMEM ; epilepsy
刊名: ACTA PHARMACOLOGICA SINICA
发表日期: 2012-11-01
DOI: 10.1038/aps.2012.118
卷: 33, 期:11, 页:1417-1423
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Chemistry, Multidisciplinary ; Pharmacology & Pharmacy
研究领域[WOS]: Chemistry ; Pharmacology & Pharmacy
关键词[WOS]: ANTIEPILEPTIC DRUGS ; CLINICAL PHARMACOKINETICS ; CONCENTRATION-TOXICITY ; VALPROATE ; MONOTHERAPY ; EFFICACY ; THERAPY ; ADULTS ; NONMEM ; MODEL
英文摘要:

Aim: To establish a population pharmacokinetics (PPK) model for lamotrigine (LTG) in Chinese children with epilepsy in order to formulate an individualized dosage guideline.

Methods: LTG steady-state plasma concentration data from therapeutic drug monitoring (TDM) were collected retrospectively from 284 patients, with a total of 404 plasma drug concentrations. LTG concentrations were determined using a HPLC method. The patients were divided into 2 groups: PPK model group (n=116) and PPK valid group (n=168). A PPK model of LTG was established with NONMEM based on the data from PPK model group according to a one-compartment model with first order absorption and elimination. To validate the basic and final model, the plasma drug concentrations of the patients in PPK model group and PPK valid group were predicted by the two models.

Results: The final regression model for LTG was as follows: CL (L/h)=1.01(star)(TBW/27.87)(0.635 star)e(-0.753 star VPA star)e(0.868 star CBZ star)e(0.633 star PB), Vd (L)= 16.7(star)(TBW/27.87). The final PPK model was demonstrated to be stable and effective in the prediction of serum LTG concentrations by an internal and external approach validation.

Conclusion: A PPK model of LTG in Chinese children with epilepsy was successfully established with NONMEM. LTG concentrations can be predicted accurately by this model. The model may be very useful for establishing initial LTG dosage guidelines.

语种: 英语
所属项目编号: 81171630
项目资助者: National Natural Science Foundation of China
WOS记录号: WOS:000310778400012
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/50060
Appears in Collections:北京大学第一临床医学院_儿科_期刊论文

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作者单位: 1.Shanghai Jiao Tong Univ, Sch Med, Xinhua Hosp, Dept Pediat, Shanghai 200092, Peoples R China
2.Peking Univ, Hosp 1, Dept Pediat, Beijing 100034, Peoples R China
3.Peking Univ, Hlth Sci Ctr, Sch Pharmaceut Sci, Beijing 100191, Peoples R China
4.Beijing Childrens Hosp, Dept Neurol, Beijing 100045, Peoples R China
5.Shanghai Jiao Tong Univ, Sch Med, Xinhua Hosp, Dept Pharm, Shanghai 200092, Peoples R China

Recommended Citation:
He, Da-ke,Wang, Li,Lu, Wei,et al. Population pharmacokinetics of lamotrigine in Chinese children with epilepsy[J]. ACTA PHARMACOLOGICA SINICA,2012,33(11):1417-1423.
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