IR@PKUHSC  > 北京大学第三临床医学院  > 呼吸科
学科主题临床医学
Pharmacokinetics and Pharmacodynamics of Meropenem in Elderly Chinese with Lower Respiratory Tract Infections Population Pharmacokinetics Analysis Using Nonlinear Mixed-Effects Modelling and Clinical Pharmacodynamics Study
Zhou, Qing-tao1; He, Bei1; Zhang, Chao2; Zhai, Suo-di2; Liu, Zhen-ying3; Zhang, Jie3
刊名DRUGS & AGING
2011
28期:11页:903-912
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Geriatrics & Gerontology ; Pharmacology & Pharmacy
研究领域[WOS]Geriatrics & Gerontology ; Pharmacology & Pharmacy
关键词[WOS]FEBRILE NEUTROPENIC PATIENTS ; HOSPITAL-ACQUIRED PNEUMONIA ; CRITICALLY-ILL PATIENTS ; INTENSIVE-CARE-UNIT ; CREATININE CLEARANCE ; PEDIATRIC-PATIENTS ; REPLACEMENT
英文摘要

Background: Meropenem is a broad-spectrum antibacterial that is usually used in the treatment of serious lower respiratory tract infections (LRTIs). However, there is a lack of published studies exploring the correlation between the population pharmacokinetics of meropenem, the clinical pharmacodynamics of the drug and the response to the drug in Chinese patients with LRTIs, especially in the elderly.

Objective: The aim of this study was to develop a pharmacokinetic model of meropenem using patient data and use this to explore the clinical pharmacodynamics of meropenem in the treatment of LRTIs in elderly Chinese patients.

Methods: We measured serum meropenem concentrations in patients who had received meropenem 0.5 or 1.0 g infused over 0.5 hours every 8 or 12 hours, respectively. The pharmacokinetic analysis of meropenem was performed using nonlinear mixed-effects modelling (NONMEM (R)) software. The minimum inhibitory concentration (MIC) of meropenem against Gram-negative bacilli was tested by the E-test method. The pharmacodynamic parameters of percentage of time above MIC (%T>MIC), the ratio of the drug area under the serum concentration-time curve to MIC (C(max)/MIC), the ratio of the maximum serum concentration of the drug to MIC (Cmax/MIC) and the ratio of the minimum serum concentration of the drug to MIC (C(min)/MIC) were analysed for their association with clinical and bacteriological outcomes.

Results: A total of 284 serum meropenem concentration measurements were obtained from 75 patients (aged 63-95 years). A two-compartment model fitted the concentration data best. The covariates creatinine clearance (CL(CR)) and Acute Physiology and Chronic Health Evaluation (APACHE) II score had the most significant effects on meropenem pharmacokinetics. Forty-five patients were enrolled in the pharmacodynamic study, including 25 clinical responders and 21 patients with bacteriological eradication. All of the 45 patients had Gram-negative bacilli isolated from tracheal aspirate or sputum. The %T>MIC, AUC/MIC, C(max)/MIC and C(min)/MIC values for the 25 clinical responders were significantly higher than those for the nonresponders (all p<0.05). However, logistic regression analysis showed that only %T>MIC independently influenced clinical outcome (p=0.001, odds ratio [OR] = 1.065). The cut-off value for predicting clinical success using %T>MIC was 76%; the sensitivity and specificity of %T>MIC for predicting a successful response were 84% and 85%, respectively. The %T>MIC, AUC/MIC, C(max)/MIC and C(min)/MIC values, and the serum level of albumin, for the 21 patients with bacteriological eradication were significantly higher than those for patients with bacteriological treatment failure (all p<0.05). Logistic regression analysis showed that %T>MIC (p=0.008, OR=1.047) and serum level of albumin (p=0.033, OR=1.434) independently influenced bacteriological eradication.

Conclusions: To our knowledge, this is the first study to investigate the population pharmacokinetics and clinical pharmacodynamics of meropenem in elderly Chinese. CL(CR) and APACHE II score have significant influences on meropenem pharmacokinetics. In LRTI patients, the cut-off value of 76% for %T>MIC can be applied to optimize their meropenem dose regimen to achieve clinical success.

语种英语
WOS记录号WOS:000297970400006
引用统计
被引频次:10[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/400002259/60150
专题北京大学第三临床医学院_呼吸科
北京大学第二临床医学院_产科
作者单位1.Peking Univ, Hosp 3, Dept Pharm, Beijing 100191, Peoples R China
2.Peking Univ, Hosp 3, Dept Resp Med, Beijing 100191, Peoples R China
3.Peking Univ, Hosp 3, Dept Clin Lab, Beijing 100191, Peoples R China
推荐引用方式
GB/T 7714
Zhou, Qing-tao,He, Bei,Zhang, Chao,et al. Pharmacokinetics and Pharmacodynamics of Meropenem in Elderly Chinese with Lower Respiratory Tract Infections Population Pharmacokinetics Analysis Using Nonlinear Mixed-Effects Modelling and Clinical Pharmacodynamics Study[J]. DRUGS &amp; AGING,2011,28(11):903-912.
APA Zhou, Qing-tao,He, Bei,Zhang, Chao,Zhai, Suo-di,Liu, Zhen-ying,&Zhang, Jie.(2011).Pharmacokinetics and Pharmacodynamics of Meropenem in Elderly Chinese with Lower Respiratory Tract Infections Population Pharmacokinetics Analysis Using Nonlinear Mixed-Effects Modelling and Clinical Pharmacodynamics Study.DRUGS & AGING,28(11),903-912.
MLA Zhou, Qing-tao,et al."Pharmacokinetics and Pharmacodynamics of Meropenem in Elderly Chinese with Lower Respiratory Tract Infections Population Pharmacokinetics Analysis Using Nonlinear Mixed-Effects Modelling and Clinical Pharmacodynamics Study".DRUGS & AGING 28.11(2011):903-912.
条目包含的文件
条目无相关文件。
个性服务
推荐该条目
保存到收藏夹
查看访问统计
导出为Endnote文件
谷歌学术
谷歌学术中相似的文章
[Zhou, Qing-tao]的文章
[He, Bei]的文章
[Zhang, Chao]的文章
百度学术
百度学术中相似的文章
[Zhou, Qing-tao]的文章
[He, Bei]的文章
[Zhang, Chao]的文章
必应学术
必应学术中相似的文章
[Zhou, Qing-tao]的文章
[He, Bei]的文章
[Zhang, Chao]的文章
相关权益政策
暂无数据
收藏/分享
所有评论 (0)
暂无评论
 

除非特别说明,本系统中所有内容都受版权保护,并保留所有权利。