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非危重症成年患者的万古霉素群体药代动力学模型:一项范围综述

Vancomycin Population Pharmacokinetic Models in Non- Critically Ill Adults Patients: a scoping review.

作者信息

Nivia Diego, Vivas Juan-David, Briceño Wilson, Parra Daniel, Mena Manuel, Jaimes Diego, Guevara Juan-Francisco, Bustos Rosa Helena

机构信息

Department of Pharmacology, Evidence-based Therapeutic Group, Faculty of Medicine, Universidad de La Sabana, Clinica Universidad de La Sabana, Chía, Cundinamarca, 140013, Colombia.

出版信息

F1000Res. 2025 Mar 6;11:1513. doi: 10.12688/f1000research.128260.2. eCollection 2022.

Abstract

BACKGROUND

Vancomycin is an effective first-line therapy primarily in methicillin-resistant Staphylococcus aureus (MRSA) infection and Clostridium difficile, however, it has been shown that its effectiveness and the reduction of nephrotoxicity depend on maintaining adequate therapeutic levels. Population pharmacokinetic (PopPk) models attempt to parameterize the behavior of plasma concentrations in different target populations and scenarios such as renal replacement therapy, to successful therapeutic outcome and avoid these side effects.

METHODS

A scoping review was conducted following the guidelines of Preferred Reporting Items for Systematic reviews and Meta-Analyses Extension for Scoping Reviews (PRISMA-ScR), through a search in PubMed, LILACS, OVID Medline, Scopus, Web of Science, SAGE Journals, Google Scholar and previous known registers of PopPk models in non-critically ill adult patients, published between 1998 and 2024.

RESULTS

A total of 190 papers were fully screened, of which were included 36 studies conducted in different populations; 12 in general population, 23 in special populations (surgical, with impaired renal function, obese, elderly, with cancer and cystic fibrosis), and 1 in mixed population (general and with cancer). The main parameters in the models were renal clearance and volume of distribution. The principal covariables that affected the models were creatinine clearance and weight. All studies used internal evaluation and 4 of them used an external group.

DISCUSSION

The technology for the development and implementation of PopPk models requires experts in clinical pharmacology and is limited to university and research centers. The software is mostly expensive and, in most cases, the pharmacokinetic models and the heterogeneity in the parameters and evaluation methods depend on which compartmental model, parameters, covariates and software have been used.

CONCLUSIONS

These models require validation in the clinical context and conducting experiments to adapt them for precision dosing in different subpopulations.

摘要

背景

万古霉素是治疗耐甲氧西林金黄色葡萄球菌(MRSA)感染和艰难梭菌的有效一线疗法,然而,研究表明其有效性及肾毒性的降低取决于维持足够的治疗水平。群体药代动力学(PopPk)模型试图对不同目标人群和场景(如肾脏替代治疗)中的血浆浓度行为进行参数化,以实现成功的治疗效果并避免这些副作用。

方法

按照系统评价和范围综述的首选报告项目扩展版(PRISMA-ScR)的指南进行范围综述,通过在PubMed、LILACS、OVID Medline、Scopus、科学网、SAGE期刊、谷歌学术以及先前已知的非危重症成年患者PopPk模型登记册中进行检索,检索时间范围为1998年至2024年。

结果

共对190篇论文进行了全面筛选,其中包括在不同人群中开展的36项研究;12项在普通人群中,23项在特殊人群(外科手术患者、肾功能受损者、肥胖者、老年人、癌症患者和囊性纤维化患者)中,1项在混合人群(普通人群和癌症患者)中。模型中的主要参数是肾清除率和分布容积。影响模型的主要协变量是肌酐清除率和体重。所有研究都采用了内部评估,其中4项研究使用了外部组。

讨论

PopPk模型的开发和实施技术需要临床药理学专家,并且仅限于大学和研究中心。该软件大多价格昂贵,而且在大多数情况下,药代动力学模型以及参数和评估方法的异质性取决于所使用的房室模型、参数、协变量和软件。

结论

这些模型需要在临床环境中进行验证,并开展实验以使其适用于不同亚组的精准给药。

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