Optimizing antibiotic dosing regimens for nosocomial pneumonia: a window of opportunity for pharmacokinetic and pharmacodynamic modeling.

IF 3.9 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Expert Opinion on Drug Metabolism & Toxicology Pub Date : 2023-01-01 DOI:10.1080/17425255.2023.2178896

Yuwei Shen, Joseph L Kuti

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引用次数: 1

Abstract

Introduction: Determining antibiotic exposure in the lung and the threshold(s) needed for effective antibacterial killing is paramount during development of new antibiotics for the treatment of nosocomial pneumonia, as these exposures directly affect clinical outcomes and resistance development. The use of pharmacokinetic and pharmacodynamic modeling is recommended by regulatory agencies to evaluate antibiotic pulmonary exposure and optimize dosage regimen selection. This process has been implemented in newer antibiotic development.

Areas covered: This review will discuss the basis for conducting pharmacokinetic and pharmacodynamic studies to support dosage regimen selection and optimization for the treatment of nosocomial pneumonia. Pharmacokinetic/pharmacodynamic data that supported recent hospital-acquired bacterial pneumonia/ventilator-associated bacterial pneumonia indications for ceftolozane/tazobactam, ceftazidime/avibactam, imipenem/cilastatin/relebactam, and cefiderocol will be reviewed.

Expert opinion: Optimal drug development requires the integration of preclinical pharmacodynamic studies, healthy volunteers and ideally patient bronchoalveolar lavage pharmacokinetic studies, Monte-Carlo simulation, and clinical trials. Currently, plasma exposure has been successfully used as a surrogate for lung exposure threshold. Future studies are needed to identify the value of lung pharmacodynamic thresholds in nosocomial pneumonia antibiotic dosage optimization.

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优化院内肺炎的抗生素剂量方案:药代动力学和药效学建模的机会之窗。

在开发治疗院内肺炎的新抗生素时，确定肺部抗生素暴露量和有效抗菌杀灭所需的阈值是至关重要的，因为这些暴露量直接影响临床结果和耐药性的发展。监管机构推荐使用药代动力学和药效学模型来评估抗生素肺部暴露和优化给药方案选择。这一过程已在较新的抗生素开发中实施。涵盖领域:本综述将讨论进行药代动力学和药效学研究的基础，以支持医院获得性肺炎治疗的剂量方案选择和优化。将回顾支持最近医院获得性细菌性肺炎/呼吸机相关细菌性肺炎适应症的药代动力学/药效学数据，这些适应症包括头孢唑氮/他唑巴坦、头孢他啶/阿维巴坦、亚胺培南/西司他汀/瑞巴坦和头孢地罗。专家意见:最佳药物开发需要整合临床前药效学研究、健康志愿者和理想的患者支气管肺泡灌洗药代动力学研究、蒙特卡洛模拟和临床试验。目前，血浆暴露已被成功地用作肺暴露阈值的替代品。需要进一步的研究来确定肺药效学阈值在院内肺炎抗生素用量优化中的价值。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Expert Opinion on Drug Metabolism & Toxicology 医学-生化与分子生物学

CiteScore

7.90

自引率

2.30%

发文量

审稿时长

4-8 weeks

期刊介绍： Expert Opinion on Drug Metabolism & Toxicology (ISSN 1742-5255 [print], 1744-7607 [electronic]) is a MEDLINE-indexed, peer-reviewed, international journal publishing review articles on all aspects of ADME-Tox. Each article is structured to incorporate the author’s own expert opinion on the scope for future development. The Editors welcome: Reviews covering metabolic, pharmacokinetic and toxicological issues relating to specific drugs, drug-drug interactions, drug classes or their use in specific populations; issues relating to enzymes involved in the metabolism, disposition and excretion of drugs; techniques involved in the study of drug metabolism and toxicology; novel technologies for obtaining ADME-Tox data. Drug Evaluations reviewing the clinical, toxicological and pharmacokinetic data on a particular drug. The audience consists of scientists and managers in the pharmaceutical industry, pharmacologists, clinical toxicologists and related professionals.