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学科主题: 临床医学
题名:
Population pharmacokinetics study of remifentanil in Chinese adult patients determined by an LC-MS/MS method
作者: Zhang, C.1,2; Zhang, L.3; Zhang, X.1,2; Yang, L.1,2; Zhai, S.1,2; Duan, L.4
关键词: remifentanil ; population pharmacokinetics ; NONMEM
刊名: INTERNATIONAL JOURNAL OF CLINICAL PHARMACOLOGY AND THERAPEUTICS
发表日期: 2008-09-01
卷: 46, 期:9, 页:477-488
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Pharmacology & Pharmacy
研究领域[WOS]: Pharmacology & Pharmacy
关键词[WOS]: LIQUID-CHROMATOGRAPHY ; HUMAN BLOOD ; DOG PLASMA ; PHARMACODYNAMICS ; EXTRACTION ; METABOLITE ; SURGERY ; RAT
英文摘要:

Objectives: The aim of this study was to construct the population pharmacokinetic model in Chinese adult patients and to characterize the factors that affect the parameters of remifentanil pharmacokinetics.

Methods: 15 patients were divided randomly into two groups: Index (modeling) group and validation group. 10 patients including 99 blood samples were in the Index group and 5 patients including 56 blood samples were in the Validation group. A LC-MS/MS method was developed to determine the whole blood concentration of remifentanil. Meanwhile, population modeling was performed using the NONMEM (nonlinear mixed-effect modeling) program with a 2-compartment pharmcokinetic model. The forward inclusion backward elimination method was used to investigate the different covariates, including age, height, total bilirubin, etc.

Results: Liquid-liquid extraction was used to extract remifentanil from the blood. The calibration curve was linear from 0.5 to 50 ng/ml and the lowest limit of quantification (LOQ) was 0.5 ng/ml. The analytical method was rapid, selective and highly sensitive. The population pharmacokinetic results indicated that total bilirubin, age, alkaline phosphatase activity and gender significantly affected the parameters of remifentanil. The estimation of CL1, V1, CL2 and V2 were 1.85 l/min, 8.471, 1.28 l/min and 29.71, respectively. The population model was validated by another group of patients indicating that the model was effective and robust.

Conclusion: The LC-MS/MS method for the quantification of remifentanil in human whole blood was rapid, selective and highly sensitive. The population model was acceptable and would be helpful for clinicians to assess the remifentanil pharmacokinetic parameters based on patient′s specific demographic characteristics.

语种: 英语
项目资助者: National High Technology Development Project
WOS记录号: WOS:000259657100005
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/62697
Appears in Collections:北京大学第三临床医学院_药剂科_期刊论文

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作者单位: 1.Peking Univ, Dept Pharm, Hosp 3, Beijing 100871, Peoples R China
2.Peking Univ, Therapeut Drug Monitoring & Clin Toxicol Ctr, Beijing 100871, Peoples R China
3.Peking Univ, Dept Anaesthesia, Hosp 3, Beijing 100871, Peoples R China
4.Peking Univ, Dept Degest, Hosp 3, Beijing 100871, Peoples R China

Recommended Citation:
Zhang, C.,Zhang, L.,Zhang, X.,et al. Population pharmacokinetics study of remifentanil in Chinese adult patients determined by an LC-MS/MS method[J]. INTERNATIONAL JOURNAL OF CLINICAL PHARMACOLOGY AND THERAPEUTICS,2008,46(9):477-488.
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