万古霉素在老年感染患者体内的群体药代动力学研究

doi:10.12092/j.issn.1009-2501.2019.02.007

中国临床药理学与治疗学 ›› 2019, Vol. 24 ›› Issue (2): 158-163.doi: 10.12092/j.issn.1009-2501.2019.02.007

万古霉素在老年感染患者体内的群体药代动力学研究

朱敏¹，张翠锋¹，过怿赟²，祝子明¹

¹宣城市人民医院药学部，宣城 242000，安徽；²皖南医学院弋矶山医院临床药学部，芜湖 241001，安徽

收稿日期:2018-08-08 修回日期:2018-08-31 出版日期:2019-02-26 发布日期:2019-03-04
通讯作者: 祝子明，男，主任药师，研究方向：药事管理。 E-mail：ziming2006@163.com
作者简介:朱敏，女，主管药师，研究方向：抗感染临床药学。 E-mail：aydxs608@163.com
基金资助:
国家自然科学基金资助项目（81173134）；皖南医学院中青年科研基金（WK2015F11）

Population pharmacokinetics of vancomycin in elderly infectious patients

ZHU Min ¹, ZHANG Cuifeng¹, GUO Yiyun², ZHU Ziming¹

¹ Department of Pharmacy,the People's Hospital of Xuancheng City, Xuancheng 242000, Anhui, China; ² Department of Clinical Pharmacy, Yijishan Hospital of Wannan Medical College, Wuhu 241000, Anhui, China

Received:2018-08-08 Revised:2018-08-31 Online:2019-02-26 Published:2019-03-04

摘要/Abstract

摘要：

目的: 建立万古霉素在老年感染疾病患者体内的群体药代动力学模型，探讨其药代动力学特征及可能的影响因素。方法:71例老年感染患者的130个稳态血药浓度监测数据纳入本次研究，应用Phoenix NLME（Version 8.0）软件中的群体模块分析万古霉素静脉滴注后的血药浓度数据，估算相关药代动力学参数及其变异情况，构建万古霉素在老年患者中的群体药代动力学模型，并对最终模型进行验证。结果:采用一房室模型拟合所收集的万古霉素血药浓度数据，表观分布容积V和药物清除率CL的群体典型值分别为33.44 L和2.16 L/h。协变量筛选结果显示，肌酐清除率Ccr对药物清除率CL有显著影响（P<0.01）。结论:本研究成功建立了万古霉素在老年感染疾病患者体内的群体药代动力学模型，最终模型可对个体药代参数做出精确的估计，Ccr对药物清除率CL有显著影响。

关键词: 万古霉素, 老年感染患者, 群体药代动力学

Abstract:

AIM: To develop a population pharmacokinetic model of vancomycin in elderly infectious patients and evaluate the effect of individual factors on the pharmacokinetics of vancomycin. METHODS: A total of 130 steady state blood vancomycin concentration monitoring data were collected from 71 cases of elderly infectious patients. Phoenix NLME (Version 8.0) software was used to assess the influence of demographic characteristics on pharmacokinetic characters of vancomycin and establish the vancomycin population pharmacokinetics model in elderly patients. Then, verify the final model. RESULTS:One-compartment model was fitted to the vancomycin concentration data. The population value of V and CL were 33.44 L and 2.16 L/h, respectively. CL was found to be significantly related to the covariate of Ccr (P<0.01). CONCLUSION: The population pharmacokinetic model of vancomycin was established successfully in elderly infectious patients. The final model could be used to provide accurate individual pharmacokinetic parameters. CL was significantly influenced by the covariate of Ccr, which showed that it is better to administer drug according individual Ccr in clinical practice.

Key words: vancomycin, elderly infectious patients, population pharmacokinetics

中图分类号:

R969.1

朱敏，张翠锋，过怿赟，祝子明. 万古霉素在老年感染患者体内的群体药代动力学研究[J]. 中国临床药理学与治疗学, 2019, 24(2): 158-163.

ZHU Min, ZHANG Cuifeng, GUO Yiyun, ZHU Ziming. Population pharmacokinetics of vancomycin in elderly infectious patients[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2019, 24(2): 158-163.

参考文献

［1］Levine DP. Vancomycin: a history［J］. Clin Infect Dis, 2006, 42 Suppl 1:S5-12.
［2］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):e18-55.
［3］Alvarez R, Lopez Cortes LE, Molina J, et al. Optimizing the clinical use of vancomycin［J］. Antimicrob Agents Chemother, 2016, 60(5):2601-2609.
［4］Jeffres MN, Isakow W, Doherty JA, et al. A retrospective analysis of possible renal toxicity associated with vancomycin in patients with health care-associated methicillin-resistant Staphylococcus aureus pneumonia［J］. Clin Ther, 2007, 29(6):1107-1115.
［5］Sakoulas G, Gold HS, Cohen RA, et al. Effects of prolonged vancomycin administration on methicillin-resistant Staphylococcus aureus (MRSA) in a patient with recurrent bacteraemia［J］. J Antimicrob Chemother, 2006, 57(4):699-704.
［6］Moise-Broder PA, Forrest A, Birmingham MC, et al. Pharmacodynamics of vancomycin and other antimicrobials in patients with Staphylococcus aureus lower respiratory tract infections［J］. Clin Pharmacokinet, 2004, 43(13):925-942.
［7］陈冰, 杨婉花, 张伟霞, 等.中国成年患者万古霉素群体药动学研究［J］. 药学与临床研究, 2013, 21(6):605-609.
［8］Boeckmann A, Sheiner L, Beal S. NONMEM Users Guide［M］. Part V: 102-103.
［9］张弨, 赵荣生, 翟所迪, 等.群体药代动力学概述［J］. 中国临床药理学杂志, 2013, 29(8):563-565.
［10］Deng C, Liu T, Zhou T, et al. Initial dosage regimens of vancomycin for Chinese adult patients based on population pharmacokinetic analysis［J］. Int J Clin Pharmacol Ther, 2013, 51(5):407-415.
［11］Purwonugroho TA, Chulavatnatol S, Preechagoon Y, et al. Population pharmacokinetics of vancomycin in Thai patients［J］. Scientific World J, 2012, 2012:762649.
［12］Llopis-Salvia P, Jimenez-Torres NV. Population pharmacokinetic parameters of vancomycin in critically ill patients［J］. J Clin Pharm Ther, 2006, 31(5):447-454.
［13］Chung JY, Jin SJ, Yoon JH, et al. Serum cystatin C is a major predictor of vancomycin clearance in a population pharmacokinetic analysis of patients with normal serum creatinine concentrations［J］. J Korean Med Sci, 2013, 28(1):48-54.
［14］Lin WW, Wu W, Jiao Z, et al. Population pharmacokinetics of vancomycin in adult Chinese patients with post-craniotomy meningitis and its application in individualised dosage regimens［J］. Eur J Clin Pharmacol, 2016, 72(1):29-37.
［15］Ji XW, Ji SM, He XR, et al. Influences of renal function descriptors on population pharmacokinetic modeling of vancomycin in Chinese adult patients［J］. Acta Pharmacol Sin, 2018, 39(2):286-293.
［16］Li X, Wu Y, Sun S, et al. Population Pharmacokinetics of Vancomycin in Postoperative Neurosurgical Patients and the Application in Dosing Recommendation［J］. J Pharm Sci, 2016, 105(11):3425-3431.
［17］翁芳娟. 万古霉素的群体药动学研究［J］. 海峡药学, 2013, 25(7):207-209.
［18］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.
［19］Moore JN, Healy JR, Thoma BN, et al. A Population Pharmacokinetic Model for Vancomycin in Adult Patients Receiving Extracorporeal Membrane Oxygenation Therapy［J］. CPT Pharmacometrics Syst Pharmacol, 2016, 5(9):495-502.
［20］杨平, 刘亚欧, 时正媛, 等.万古霉素在重症监护患者的群体药代动力学模型建立与验证［J］. 中国临床药理学杂志, 2018，34(6)：656-659.

[1]	李梦雪, 何杰, 余霞霞, 胡琳璘, 邵华. 利妥昔单抗群体药代动力学研究进展[J]. 中国临床药理学与治疗学, 2023, 28(4): 468-474.
[2]	吴莉莉, 梁至, 黄思咏, 王妍. 肾功能亢进对感染性心内膜炎患者万古霉素药动学的影响及有效性与安全性研究[J]. 中国临床药理学与治疗学, 2023, 28(10): 1139-1145.
[3]	徐涛, 朱素燕, 邱相君, 徐萍. 肾功能不全患者人群中替考拉宁群体药代动力学模型的建立与验证[J]. 中国临床药理学与治疗学, 2022, 27(9): 977-983.
[4]	林良沫, 符祥俊, 钟莉莉, 王和芳, 吴琼诗, 肖坚. 中性粒细胞缺乏患者万古霉素群体药代动力学模型的建立[J]. 中国临床药理学与治疗学, 2021, 26(9): 1014-1022.
[5]	符祥俊, 黄莉, 郭丽, 林良沫. 万古霉素AUC/MIC在多重耐药革兰阳性菌致重症感染中的应用分析[J]. 中国临床药理学与治疗学, 2021, 26(7): 775-781.
[6]	徐国防, 张思森, 刘平, 梅家转, 刘玮玮, 刘亚欧, 齐琦. 卡培他滨在中国乳腺癌患者中的群体药代动力学研究[J]. 中国临床药理学与治疗学, 2021, 26(5): 552-559.
[7]	李文超, 白向荣, 李晓玲, 姜德春. 替加环素在治疗感染性疾病中的群体药代动力学/药效学研究进展[J]. 中国临床药理学与治疗学, 2021, 26(11): 1265-1272.
[8]	郭仙忠, 林荣芳, 林玮玮. 基于群体药动学模型的万古霉素个体化给药软件研制及应用[J]. 中国临床药理学与治疗学, 2021, 26(1): 30-39.
[9]	李健, 杨进波, 王玉珠. 创新药群体药代动力学研究申报资料的探讨[J]. 中国临床药理学与治疗学, 2020, 25(5): 546-549.
[10]	陈文君，阮邹荣，相小强. 生理药代动力学模型的发展应用动态及其与其他建模方法的融合[J]. 中国临床药理学与治疗学, 2020, 25(3): 299-305.
[11]	李健，杨进波，王玉珠. 模型引导的药物开发在新药研发中的应用[J]. 中国临床药理学与治疗学, 2020, 25(1): 1-8.
[12]	吴敏，过怿赟，谢海棠. 乳腺癌患者体内他莫昔芬的群体药代动力学研究[J]. 中国临床药理学与治疗学, 2019, 24(4): 418-423.
[13]	牛姝，梁立宇，徐凤艳，顾晓玲，王鲲，邵建华，孙继佳，黄继汉. 儿童药动学试验设计的样本量与采样点数的模拟探索[J]. 中国临床药理学与治疗学, 2018, 23(4): 413-421.
[14]	陈曜曜，史道华，刘光华，牛培广，刘柏晨. OCT2、MDR1基因多态性与婴幼儿万古霉素血药浓度及临床疗效的相关性研究[J]. 中国临床药理学与治疗学, 2018, 23(2): 154-158.
[15]	丁志荣，蔡晓祯，曾海文，林天来. 万古霉素在神经外科开颅术后患者颅内的群体药代动力学[J]. 中国临床药理学与治疗学, 2018, 23(11): 1252-1257.

万古霉素在老年感染患者体内的群体药代动力学研究

Population pharmacokinetics of vancomycin in elderly infectious patients

PDF (PC)

可视化

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 15

编辑推荐

Metrics

本文评价