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学科主题临床医学
Population pharmacokinetics study of remifentanil in Chinese adult patients determined by an LC-MS/MS method
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
2008-09-01
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
WOS记录号WOS:000259657100005
引用统计
被引频次:6[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/62697
专题北京大学第三临床医学院_药剂科
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
推荐引用方式
GB/T 7714
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.
APA Zhang, C.,Zhang, L.,Zhang, X.,Yang, L.,Zhai, S.,&Duan, L..(2008).Population pharmacokinetics study of remifentanil in Chinese adult patients determined by an LC-MS/MS method.INTERNATIONAL JOURNAL OF CLINICAL PHARMACOLOGY AND THERAPEUTICS,46(9),477-488.
MLA Zhang, C.,et al."Population pharmacokinetics study of remifentanil in Chinese adult patients determined by an LC-MS/MS method".INTERNATIONAL JOURNAL OF CLINICAL PHARMACOLOGY AND THERAPEUTICS 46.9(2008):477-488.
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