Dose Individualisation of Antimicrobials from a Pharmacometric Standpoint: The Current Landscape.

IF 13 1区 医学 Q1 PHARMACOLOGY & PHARMACY Drugs Pub Date : 2024-10-01 Epub Date: 2024-09-06 DOI:10.1007/s40265-024-02084-7
Tim Preijers, Anouk E Muller, Alan Abdulla, Brenda C M de Winter, Birgit C P Koch, Sebastiaan D T Sassen
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Abstract

Successful antimicrobial therapy depends on achieving optimal drug concentrations within individual patients. Inter-patient variability in pharmacokinetics (PK) and differences in pathogen susceptibility (reflected in the minimum inhibitory concentration, [MIC]) necessitate personalised approaches. Dose individualisation strategies aim to address this challenge, improving treatment outcomes and minimising the risk of toxicity and antimicrobial resistance. Therapeutic drug monitoring (TDM), with the application of population pharmacokinetic (popPK) models, enables model-informed precision dosing (MIPD). PopPK models mathematically describe drug behaviour across populations and can be combined with patient-specific TDM data to optimise dosing regimens. The integration of machine learning (ML) techniques promises to further enhance dose individualisation by identifying complex patterns within extensive datasets. Implementing these approaches involves challenges, including rigorous model selection and validation to ensure suitability for target populations. Understanding the relationship between drug exposure and clinical outcomes is crucial, as is striking a balance between model complexity and clinical usability. Additionally, regulatory compliance, outcome measurement, and practical considerations for software implementation will be addressed. Emerging technologies, such as real-time biosensors, hold the potential for revolutionising TDM by enabling continuous monitoring, immediate and frequent dose adjustments, and near patient testing. The ongoing integration of TDM, advanced modelling techniques, and ML within the evolving digital health care landscape offers a potential for enhancing antimicrobial therapy. Careful attention to model development, validation, and ethical considerations of the applied techniques is paramount for successfully optimising antimicrobial treatment for the individual patient.

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从药物计量学角度看抗菌药物的剂量个体化:当前形势。
成功的抗菌治疗取决于能否在个体患者体内达到最佳药物浓度。患者之间的药代动力学(PK)差异和病原体敏感性差异(反映在最低抑菌浓度上)使得个性化治疗成为必要。剂量个体化策略旨在应对这一挑战,改善治疗效果,最大限度地降低毒性和抗菌药耐药性风险。通过应用群体药代动力学(popPK)模型进行治疗药物监测(TDM),可实现以模型为依据的精确用药(MIPD)。PopPK 模型从数学角度描述了不同人群的用药行为,并可与特定患者的 TDM 数据相结合,优化用药方案。机器学习(ML)技术的整合有望通过识别大量数据集中的复杂模式,进一步加强剂量个体化。实施这些方法面临着挑战,包括严格的模型选择和验证,以确保适合目标人群。了解药物暴露与临床结果之间的关系至关重要,在模型复杂性与临床可用性之间取得平衡也同样重要。此外,还将讨论监管合规性、结果测量和软件实施的实际考虑因素。实时生物传感器等新兴技术通过实现连续监测、即时和频繁的剂量调整以及就近病人测试,有可能彻底改变 TDM。在不断发展的数字医疗保健领域,TDM、先进建模技术和 ML 的不断融合为加强抗菌治疗提供了潜力。要想成功优化针对个体患者的抗菌治疗,就必须对应用技术的模型开发、验证和伦理考虑给予认真关注。
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来源期刊
Drugs
Drugs 医学-毒理学
CiteScore
22.70
自引率
0.90%
发文量
134
审稿时长
3-8 weeks
期刊介绍: Drugs is a journal that aims to enhance pharmacotherapy by publishing review and original research articles on key aspects of clinical pharmacology and therapeutics. The journal includes: Leading/current opinion articles providing an overview of contentious or emerging issues. Definitive reviews of drugs and drug classes, and their place in disease management. Therapy in Practice articles including recommendations for specific clinical situations. High-quality, well designed, original clinical research. Adis Drug Evaluations reviewing the properties and place in therapy of both newer and established drugs. AdisInsight Reports summarising development at first global approval. Moreover, the journal offers additional digital features such as animated abstracts, video abstracts, instructional videos, and podcasts to increase visibility and educational value. Plain language summaries accompany articles to assist readers with some knowledge of the field in understanding important medical advances.
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