下呼吸道感染重症患者万古霉素群体药代动力学研究

杨薇; 贺蓓; 邓晨辉

doi:10.3760/cma.j.issn.1001-0939.2017.03.012

高级检索

IP登录

登录IP

切换

退出

中华结核和呼吸杂志

• 论著 •

ENGLISH ABSTRACT

下呼吸道感染重症患者万古霉素群体药代动力学研究

作者及单位信息

出版日期： 2017 -03 -12 ·

DOI： 10.3760/cma.j.issn.1001-0939.2017.03.012

Population pharmacokinetics of vancomycin from severe in patients with lower respiratory tract infection

Authors Info & Affiliations

Yang Wei

Department of Respiratory Medicine, Peking University Third Hospital, Beijing 100191, China

He Bei

Deng Chenhui

Published： 2017 -03 -12 ·

DOI： 10.3760/cma.j.issn.1001-0939.2017.03.012

970

APP内阅读

摘要

目的探讨下呼吸道感染重症患者万古霉素群体药代动力学(PPK)，为重症患者万古霉素的个体化治疗提供依据。

方法收集2011年11月至2012年11月在我院呼吸科普通病房和呼吸科ICU(RICU)住院的下呼吸道感染同时使用万古霉素治疗的重症患者。留取万古霉素给药结束后不同时间点的血标本，用高效液相色谱分析方法检测血清药物浓度。采用非线性混合效应模型法建立万古霉素PPK模型。

结果患者70例，男58例，女12例；年龄23～91岁，平均78岁；急性生理学及慢性健康状况评分(APACHⅡ)平均为(16.4±4.8)分。检测万古霉素血清药物浓度标本267份。万古霉素的血药浓度－时间数据符合二室模型；NONMEM法建立万古霉素PPK的最终模型为CL _i＝1.67×e ^η1，V _1i＝33.04×[1－0.199×(60/Scr)]×e ^η2，Q _i＝7.08×2.053 ^AI×e ^η3，V _2i＝19.29×e ^η4。其中CL _i、V _1i、Q _i和V _2i分别指个体万古霉素的清除率、中央隔室表观分布容积、药物中央隔室与周边隔室的转换速率、周边隔室的表观分布容积；群体典型值分别为1.7 L/h、33.0 L、7.08 L/h、19.29 L。血肌酐中位值每变化1个单位，V ₁的校正幅度为19.9%；输入白蛋白患者的Q值为未输入白蛋白患者的2.1倍。

结论重症下呼吸道感染的患者血清肌酐水平和白蛋白水平是影响万古霉素PPK的因素。肾功能障碍可导致药物清除半衰期延长，应调整给药方案。输注白蛋白不影响万古霉素给药方案，但低蛋白血症患者输注白蛋白可能缩短药物到达肺组织的时间。

关键词：抗甲氧西林金黄色葡萄球菌;万古霉素;药代动力学

ABSTRACT

ObjectiveTo develop a population pharmacokinetic (PPK) model of vancomycin in Chinese inpatients with severe lower respiratory tract infection.

MethodsWe gathered serum concentrations of vancomycin from inpatients who received vancomycin during Nov 2011 to Nov 2012.Vancomycin serum concentrations was measured by high performance liquid chromatography. Vancomycin PPK analysis was performed using nonlinear mixed effects model (NONMEM) program.

ResultsWe gathered the data of 70 inpatients with lower respiratory tract infection at respiratory ward or respiratory intensive care unit(RICU) between Nov 2011 to Nov 2012 [58 males, 12 females; 78(23-91) years old; the mean of APACHⅡ score was 16.4±4.8]. A total of 267 concentrations of vancomycin were gathered from 70 patients. A 2-compartment model fit the concentration data best. The final vancomycin PPK model was: CL _i=1.67×e ^η1, V _1i=33.04×[1-0.199×(60/Scr)] ×e ^η2, Q _i=7.08×2.053 ^AI×e ^η3, V _2i=19.29×e ^η4.(CL: vancomycin clearance; V ₁: distribution volume of the central compartment; Q: intercompartment clearance; V ₂: distribution volume of the intercompartment). The population mean values were 1.67 L/h, 33.04 L; 7.08 L/h and 19.29 L respectively. Serum creatinine was the covariate to affect vancomycin apparent distribution volume of the central compartment. Intercompartment clearance was 2.053 times larger in patients with albumin infusion than that in patients without.

ConclusionsWe found that a 2-compartment model fit the concentration data best in Chinese patients with severe lower respiratory tract infection. Serum creatinine and albumin infusion were the most significant covariates to affect vancomycin PK.

KEYWORDS： Staphylococcus aureus;Vancomycin;Pharmacokinetics

Corresponding author:He Bei, Email: nc.defudabe.umjbbh_3hup

FUNDING:

Capital Development Fund(2009-2025)

COPYRIGHTS:

No content published by the journals of Chinese Medical Association may be reproduced or abridged without authorization. Please do not use or copy the layout and design of the journals without permission.

All articles published represent the opinions of the authors, and do not reflect the official policy of the Chinese Medical Association or the Editorial Board, unless this is clearly specified.

引用本文

杨薇,贺蓓,邓晨辉. 下呼吸道感染重症患者万古霉素群体药代动力学研究[J]. 中华结核和呼吸杂志,2017,40(3)：205-209.

DOI:10.3760/cma.j.issn.1001-0939.2017.03.012

PERMISSIONS

Request permissions for this article from CCC.

评价本文

*以上评分为匿名评价

版权归中华医学会所有。

未经授权，不得转载、摘编本刊文章，不得使用本刊的版式设计。

除非特别声明，本刊刊出的所有文章不代表中华医学会和本刊编委会的观点。

耐甲氧西林金黄色葡萄球菌(methicillin－resistant staphylococcus aureus，MRSA)是目前社区和医院获得性肺炎的主要病原菌之一。自1956年万古霉素问世以来依然是指南推荐治疗MRSA的一线首选药物 ^{[
1
]}。2011年美国感染疾病协会(the Infectious Diseases Society of America ，IDSA)制定的MRSA感染治疗指南中指出，重症感染患者需监测万古霉素谷浓度，以指导万古霉素剂量的调整。但谷浓度监测需要在给药4～5次达到稳态血药浓度时进行，有可能导致因为初始剂量不当而影响患者疗效。群体药代动力学(population pharmaco－kinetics，PPK)模型克服了传统药代动力学(PK)在健康志愿者中进行的缺陷，其结合患者的病理、生理学参数计算出每个个体的初始给药剂量和方案，从而通过及时合理给药改善患者的预后。PPK模型可能因为研究人群基础疾病不同、疾病严重程度不同、人种不同及感染类型不同而有差异 ^{[
2
,

3
,

4
]}。但已经报告的PPK模型绝大部分来自于血流感染人群，尚无下呼吸道感染人群的万古霉素PPK模型，目前也无万古霉素在我国人群PPK的研究报道。本研究建立在我国住院下呼吸道感染重症患者万古霉素PPK模型，为在我国人群中实现万古霉素个体化给药方案提供依据，对优化该药在临床中的使用提供帮助。

试读结束，您可以通过登录机构账户或个人账户后获取全文阅读权限。

已是订阅账户? 登录

摘要
参考文献

参考文献

[1]

Liu C , Bayer A , Cosgrove SE ,et al. Clinical practice guidelines by the infectious diseases society of america for the treatment of methicillin－resistant Staphylococcus aureus infections in adults and children[J]. Clin Infect Dis， 2011，52(3):e18－e55. DOI: 10.1093/cid/ciq146 .

返回引文位置Google Scholar

百度学术

万方数据

[2]

Dolton M , Xu H , Cheong E ,et al. Vancomycin pharmacokinetics in patients with severe burn injuries[J]. Burns, 2010，36(4)：469－476. DOI: 10.1016/j.burns.2009.08.010 .

返回引文位置Google Scholar

百度学术

万方数据

[3]

Yamamoto M , Kuzuya T , Baba H ,et al. Population pharmacokinetic analysis of vancomycin in patients with gram－positive infections and the influence of infectious disease type[J]. J Clin Pharm Ther, 2009，34(4)：473－483. DOI: 10.1111/j.1365-2710.2008.01016.x .

返回引文位置Google Scholar

百度学术

万方数据

[4]

Roberts JA , Taccone FS , Udy AA ,et al. Vancomycin dosing in critically ill patients: robust methods for improved continuous－infusion regimens[J]. Antimicrob Agents Chemother, 2011，55(6)：2704－2709. DOI： 10.1128/AAC.01708-10 .

返回引文位置Google Scholar

百度学术

万方数据

[5]

Woodhead M , Blasi F , Ewig S ，et al. Guidelines for the management of adult lower respiratory tract infections－Summary[J]. Clin Microbiol Infect， 2011，17(Suppl 6)：1－24. DOI： 10.1111/j.1469-0691.2011.03602.x .

返回引文位置Google Scholar

百度学术

万方数据

[6]

Tanaka A , Aiba T , Otsuka T ,et al. Population pharmacokinetic analysis of vancomycin using serum cystatin C as a marker of renal function[J]. Antimicrob Agents Chemother， 2010，54(2)：778－782. DOI： 10.1128/AAC.00661-09 .

返回引文位置Google Scholar

百度学术

万方数据

[7]

Zhang J , Zhang Y , Shi Y ,et al. Population pharmacokinetic and pharmacodynamics modeling of norvancomycin[J]. Eur J Clin Microbiol Infect Dis， 2008，27(4)；275－284. DOI： 10.1007/s10096-007-0435-9 .

返回引文位置Google Scholar

百度学术

万方数据

[8]

Llopis－Salvia P , Jinenez－Torres NV . Population pharmacokinetic parameters of vancomycin in critically ill patients[J]. J Clin Pharm Ther， 2006，31(5)：447－454. DOI： 10.1111/j.1365-2710.2006.00762.x .

返回引文位置Google Scholar

百度学术

万方数据

[9]

Mulla H , Pooboni S . Population pharmacokinetics of vancomycin in patients receiving extracorporeal membrane oxygenation[J]. Br J Clin Pharmacol， 2005，60(3)：265－275. DOI： 10.1111/j.1365-2125.2005.02432.x .

返回引文位置Google Scholar

百度学术

万方数据

[10]

Yasuhara M , Iga T , Zenda H ,et al. Population pharmacokinetics of vancomycin in Janpanese adult patients[J]. Ther Drug Monit, 1998，20(2)：139－148.

返回引文位置Google Scholar

百度学术

万方数据

[11]

Purwonugroho TA , Chulavatnatol S , Preechagoon Y ,et al. Population pharmacokinetics of vancomycin in Thai patients[J]. Scientific World J， 2012，2012：762649. DOI： 10.1100/2012/762649 .

返回引文位置Google Scholar

百度学术

万方数据

备注信息

通信作者：贺蓓，Email： nc.defudabe.umjbbh_3hup

基金项目：

首都发展基金重点项目 (2009－2025) 查看更多基金信息

评论 （0条）

暂无评论，发表第一条评论抢沙发