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中国临床药理学与治疗学 ›› 2023, Vol. 28 ›› Issue (10): 1139-1145.doi: 10.12092/j.issn.1009-2501.2023.10.007

• 临床药理学 • 上一篇    下一篇

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

吴莉莉1,梁  至2,黄思咏3,王  妍1   

  1. 1佛山市第一人民医院药学部,佛山  528000,广东;
    2广州市第一人民医院临床药学科,广州  510180,广东;
    3广东药科大学附属第一医院临床药学重点专科,广州  510080,广东
  • 收稿日期:2023-04-20 修回日期:2023-08-11 出版日期:2023-10-26 发布日期:2023-10-26
  • 通讯作者: 王妍,女,博士,主任药师,研究方向:医院药事管理。 E-mail:77565663@qq.com
  • 作者简介:吴莉莉,女,博士,主管药师,研究方向:临床药学和治疗药物监测。 E-mail:xnwll668@126.com
  • 基金资助:
    广东省基础与应用基础研究基金区域联合基金-青年基金项目(2021A1515110289);广东省中医药局面上项目(20241299)

Effect of augmented renal clearance (ARC) on the pharmacokinetics, efficacy, and safety of vancomycin in patients with infective endocarditis

WU Lili1, LIANG Zhi2, HUANG Siyong3, WANG Yan1   

  1. 1Department of Pharmacy, The First People's Hospital of Foshan, Foshan 528000, Guangdong, China; 2Department of Clinical Pharmacy, Guangzhou First People's Hospital, South China University of Technology, Guangzhou 510180, Guangdong, China; 3Key Specialty of Clinical Pharmacy, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou 510080, Guangdong, China 
  • Received:2023-04-20 Revised:2023-08-11 Online:2023-10-26 Published:2023-10-26

摘要: 目的:分析肾功能亢进(ARC)对感染性心内膜炎患者万古霉素药动学、有效性及安全性的影响,以提供更好的用药指导。方法:回顾性分析2020年4月至2023年4月静脉使用万古霉素的感染性心内膜炎患者的临床资料和稳态谷浓度数据,根据肾小球滤过率(eGFR)将患者分为正常组和ARC组,采用Bayesian反馈法估算药动学参数并分析ARC对万古霉素药动学的影响。结果:本研究共纳入163例患者,其中有38例患者存在ARC(发生率为23.31%),ARC组患者年龄显著低于正常组(P<0.05)。ARC组患者万古霉素谷浓度(Cmin)、谷浓度达标率、药时曲线下面积(AUC)和消除半衰期(t1/2)显著低于正常组(P<0.05),而药物清除率及消除速率明显高于正常组(P<0.05)。相关性分析表明万古霉素AUC 与Cmin呈正相关性:正常组(r2=0.943,P<0.01),ARC 组(r2=0.918,P<0.01)。正常组和ARC组万古霉素AUC>400 mg·h·L-1所对应的谷浓度阈值分别为12.78 mg/L和13.32 mg/L。两组患者的临床有效率比较差异无统计学意义,正常组与ARC组患者中分别有15例和8例患者出现不良反应。结论:ARC可显著影响感染性心内膜炎患者万古霉素谷浓度、谷浓度达标率及药动学过程,建议跟据患者肾功能状态和治疗药物监测结果调整和优化给药方案,促进个体化治疗。

关键词: 万古霉素, 治疗药物监测, 肾功能亢进, 药代动力学, 感染性心内膜炎

Abstract:

AIM: To study the effects of augmented renal clearance (ARC) on vancomycin pharmacokinetics, efficacy, and safety in patients with infective endocarditis, so as to provide better guidance for vancomycin medication. METHODS: The retrospective analysis was conducted. Patients data from the hospital medical record system from April 2020 to April 2023 during the cardiovascular surgery with use of vancomycin were collected. The subjects were divided into normal group and ARC group according to glomerular filtration rate (eGFR). According to the population pharmacokinetic model, the measured trough concentration was used for a Bayesian approach to estimate individual pharmacokinetic parameters and analyze influence of ARC on vancomycin pharmacokinetics. RESULTS: A total of 163 patients were included in this study. The incidence of ARC was 23.31%. The age of patients in ARC group was significantly lower than that in normal group  (P<0.05).  Moreover, the steady-state trough concentration (Cmin), trough concentration compliance rate, area under the curve (AUC), and elimination half life (t1/2) were significantly lower in ARC group than that in normal group (P<0.05). In addition, ARC group had significantly higher clearance (CL) and elimination rate than normal group (P<0.05). Correlation analysis showed that Cmin was positively correlated with AUC (r2=0.943, P<0.01 in normal group; r2 = 0.918, P<0.01 in ARC group). The trough concentration threshold corresponding to AUC> 400 mg·h·L-1 in normal group and ARC group were 12.78 mg/L and 13.32 mg/L, respectively. There was no significant difference in terms of clinical effectiveness between the two groups. Adverse reactions occurred in 15 patients in the normal group and 8 patients in the ARC group. CONCLUSION: ARC significantly affects the trough concentration, trough concentration compliance rate, and pharmacokinetic process of vancomycin  in patients with infective endocarditis. It is recommended to monitor and optimize vancomycin dosage regimen in patients with  infective endocarditis according to different renal function status and therapeutic drug monitoring for the purpose to facilitate individualized treatment.

Key words: vancomycin, therapeutic drug monitoring, ARC, pharmacokinetics, infective endocarditis 

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