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学科主题: 临床医学
题名:
Population pharmacokinetics modeling of levetiracetam in Chinese children with epilepsy
作者: Wang, Ying-hui1; Wang, Li1; Lu, Wei2; Shang, De-wei2; Wei, Min-ji1; Wu, Ye1
关键词: levetiracetam ; epilepsy ; population pharmacokinetics ; pediatric ; Chinese children
刊名: ACTA PHARMACOLOGICA SINICA
发表日期: 2012-06-01
DOI: 10.1038/aps.2012.57
卷: 33, 期:6, 页:845-851
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]: REFRACTORY PARTIAL SEIZURES ; ADD-ON THERAPY ; HPLC-UV ; VALPROATE ; PLASMA ; DRUGS
英文摘要:

Aim: To establish a population pharmacokinetics (PPK) model of levetiracetam in Chinese children with epilepsy.

Methods: A total of 418 samples from 361 epileptic children in Peking University First Hospital were analyzed. These patients were divided into two groups: the PPK model group (n=311) and the PPK validation group (n=50). Levetiracetam concentrations were determined by HPLC. The PPK model of levetiracetam was established using NONMEM, according to a one-compartment model with first-order absorption and elimination. To validate the model, the mean prediction error (MPE), mean squared prediction error (MSPE), root mean-squared prediction error (RMSPE), weight residues (WRES), and the 95% confidence intervals (95% CI) were calculated.

Results: A regression equation of the basic model of levetiracetam was obtained, with clearance (CL/F)=0.988 L/h, volume of distribution (V/F)=12.3 L, and K-a=1.95 h(-1). The final model was as follows: K-a=1.56 V/F=12.1 (L), CL/F=1.04x(WEIG/25)(0.563)(L/h). For the basic model, the MPE, MSPE, RMSPE, WRES, and the 95%CI were 9.834 (-0.587-197.720), 50.919 (0.012-1286.429), 1.680 (0.021-34.184), and 0.0621 (-1.100-1.980). For the final model, the MPE, MSPE, RMSPE, WRES, and the 95% CI were 0.199 (-0.369-0.563), 0.002082 (0.00001-0.01054), 0.0293 (0.001-0.110), and 0.153 (-0.030-1.950).

Conclusion: A one-compartment model with first-order absorption adequately described the levetiracetam concentrations. Body weight was identified as a significant covariate for levetiracetam clearance in this study. This model will be valuable to facilitate individualized dosage regimens.

语种: 英语
所属项目编号: 2009-2021
项目资助者: UCB Pharma (Braine-l&prime ; Alleud, Belgium) ; Capital Development Fund of Medical Research of China
WOS记录号: WOS:000305034500017
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/52490
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.Peking Univ, Hosp 1, Dept Pediat, Beijing 100034, Peoples R China
2.Peking Univ, Dept Pharmaceut, Sch Pharmaceut Sci, Beijing 100191, Peoples R China

Recommended Citation:
Wang, Ying-hui,Wang, Li,Lu, Wei,et al. Population pharmacokinetics modeling of levetiracetam in Chinese children with epilepsy[J]. ACTA PHARMACOLOGICA SINICA,2012,33(6):845-851.
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