Center for Pharmacometrics and Systems Pharmacology, Department of Pharmaceutics, College of Pharmacy, University of Florida, Orlando, Florida, USA
Centre for Antimicrobial Pharmacodynamics, Department of Molecular and Clinical Pharmacology, Institute of Translational Medicine, University of Liverpool, Liverpool, United Kingdom.
Antimicrob Agents Chemother. 2019 Apr 25;63(5). doi: 10.1128/AAC.02307-18. Print 2019 May.
In June 2017, the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health, organized a workshop entitled "Pharmacokinetics-Pharmacodynamics (PK/PD) for Development of Therapeutics against Bacterial Pathogens." The aims were to discuss details of various PK/PD models and identify sound practices for deriving and utilizing PK/PD relationships to design optimal dosage regimens for patients. Workshop participants encompassed individuals from academia, industry, and government, including the United States Food and Drug Administration. This and the accompanying review on clinical PK/PD summarize the workshop discussions and recommendations. Nonclinical PK/PD models play a critical role in designing human dosage regimens and are essential tools for drug development. These include and efficacy models that provide valuable and complementary information for dose selection and translation from the laboratory to human. It is crucial that studies be designed, conducted, and interpreted appropriately. For antibacterial PK/PD, extensive published data and expertise are available. These have been leveraged to develop recommendations, identify common pitfalls, and describe the applications, strengths, and limitations of various nonclinical infection models and translational approaches. Despite these robust tools and published guidance, characterizing nonclinical PK/PD relationships may not be straightforward, especially for a new drug or new class. Antimicrobial PK/PD is an evolving discipline that needs to adapt to future research and development needs. Open communication between academia, pharmaceutical industry, government, and regulatory bodies is essential to share perspectives and collectively solve future challenges.
2017 年 6 月，美国国立卫生研究院下属的过敏与传染病研究所组织了一场题为“用于治疗细菌性病原体的治疗药物的药代动力学-药效学（PK/PD）”的研讨会。目的是讨论各种 PK/PD 模型的细节，并确定获得和利用 PK/PD 关系以设计患者最佳剂量方案的合理做法。研讨会参与者包括来自学术界、工业界和政府的个人，其中包括美国食品和药物管理局。本篇临床 PK/PD 综述总结了研讨会的讨论和建议。非临床 PK/PD 模型在设计人体剂量方案中起着至关重要的作用，是药物开发的重要工具。这些模型包括药效学和药代动力学模型，为剂量选择和从实验室到人体的转化提供了有价值的补充信息。重要的是要适当设计、进行和解释研究。对于抗菌 PK/PD，已经有大量的已发表数据和专业知识可供利用。这些已被用于制定建议、确定常见陷阱，并描述各种非临床感染模型和转化方法的应用、优势和局限性。尽管有这些强大的工具和已发表的指导，表征非临床 PK/PD 关系可能并不简单，特别是对于新药或新类别。抗菌 PK/PD 是一个不断发展的学科，需要适应未来的研究和开发需求。学术界、制药行业、政府和监管机构之间的公开沟通对于分享观点和共同解决未来的挑战至关重要。
