Preclinical Pharmacokinetic/Pharmacodynamic Studies and Clinical Trials in the Drug Development Process of EMA-Approved Antibacterial Agents: A Review
Abstract
Development of new antibacterial agents is necessary as drug-resistant bacteria are a threat to global health. In Europe, the European Medicines Agency has been guiding this development process for more than two decades. We investigated preclinical and clinical pre-approval studies to illuminate the current authorization process with emphasis on pharmacokinetic/pharmacodynamic approaches and clinical phases. All centrally authorized systemic antibacterial and antimycobacterial drugs within the European Union were included without any time restriction. Additionally, US Food and Drug Administration-approved antibiotics of the previous 3 years, which were not yet approved by the European Medicines Agency, were included. We focused on preclinical pharmacokinetic/pharmacodynamic studies and phase II and phase III clinical trials. Furthermore, we looked at the recommended dosing regimens and approved indications. In this review, we designed tree diagrams as a new means of illustrating the development process of antibiotics to relate pharmacokinetic/pharmacodynamic phase II and III studies to approved indications. We included 23 (European Medicines Agency, 18; US Food and Drug Administration, 5) antimicrobial agents. Tetracyclines, carbapenems, and cephalosporins were the leading classes. The recommended dosing intervals were significantly shorter in time- vs exposure-dependent drugs (median 8 vs 12, p = 0.006). The majority of approved indications (i.e., acute bacterial skin and…
Read the paper
Related studies
- Pharmacokinetic aspects of retinal drug delivery
- A standardised method for interpreting the association between mutations and phenotypic drug resistance in Mycobacterium tuberculosis
- From Therapeutic Drug Monitoring to Model‐Informed Precision Dosing for Antibiotics
- Capsaicin, a novel inhibitor of the NorA efflux pump, reduces the intracellular invasion of Staphylococcus aureus
- In Vitro Pharmacodynamic Evaluation of the Mutant Selection Window Hypothesis Using Four Fluoroquinolones against Staphylococcus aureus
- Discovery of Potent, Selective Multidrug and Toxin Extrusion Transporter 1 (MATE1, SLC47A1) Inhibitors Through Prescription Drug Profiling and Computational Modeling
Go deeper in Evidence Hub
Evidence Hub adds a study data sheet (design, sample size, evidence level, key numbers), an AI summary and a chat grounded in the paper's text.