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Translational PK/PD for the Development of Novel Antibiotics—A Drug Developer’s Perspective
- Source :
- Antibiotics, Vol 13, Iss 1, p 72 (2024)
- Publication Year :
- 2024
- Publisher :
- MDPI AG, 2024.
-
Abstract
- Antibiotic development traditionally involved large Phase 3 programs, preceded by Phase 2 studies. Recognizing the high unmet medical need for new antibiotics and, in some cases, challenges to conducting large clinical trials, regulators created a streamlined clinical development pathway in which a lean clinical efficacy dataset is complemented by nonclinical data as supportive evidence of efficacy. In this context, translational Pharmacokinetic/Pharmacodynamic (PK/PD) plays a key role and is a major contributor to a “robust” nonclinical package. The classical PK/PD index approach, proven successful for established classes of antibiotics, is at the core of recent antibiotic approvals and the current antibacterial PK/PD guidelines by regulators. Nevertheless, in the case of novel antibiotics with a novel Mechanism of Action (MoA), there is no prior experience with the PK/PD index approach as the basis for translating nonclinical efficacy to clinical outcome, and additional nonclinical studies and PK/PD analyses might be considered to increase confidence. In this review, we discuss the value and limitations of the classical PK/PD approach and present potential risk mitigation activities, including the introduction of a semi-mechanism-based PK/PD modeling approach. We propose a general nonclinical PK/PD package from which drug developers might choose the studies most relevant for each individual candidate in order to build up a “robust” nonclinical PK/PD understanding.
Details
- Language :
- English
- ISSN :
- 20796382
- Volume :
- 13
- Issue :
- 1
- Database :
- Directory of Open Access Journals
- Journal :
- Antibiotics
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.8b350f65cd544b579d8799292ca67984
- Document Type :
- article
- Full Text :
- https://doi.org/10.3390/antibiotics13010072