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How preclinical infection models help define antibiotic doses in the clinic
- Source :
- International journal of antimicrobial agents. 56(2)
- Publication Year :
- 2020
-
Abstract
- Appropriate dosing of antibiotics is key in the treatment of bacterial infections to ensure clinical efficacy while avoiding toxic drug concentrations and minimizing emergence of resistance. As collection of sufficient clinical evidence is difficult for specific patient populations, infection types and pathogens, market authorization, dosing strategies and recommendations often rely on data obtained from in vitro and animal experiments. The aim of this review is to provide an overview of commonly used preclinical infection models, including their strengths and limitations. In vitro, static and dynamic time-kill experiments are the most frequently used methods for assessing pharmacokinetic/pharmacodynamic (PK/PD) associations. Limitations of in vitro models include the inability to account for the effects of the immune system, and uncertainties in clinically relevant bacterial concentrations, growth conditions and the implications of emerging resistant bacterial populations during experiments. Animal experiments, most commonly murine lung and thigh infections models, are considered a necessary link between in vitro data and the clinical situation. However, there are differences in pathophysiology, immunology, and PK between species. Mathematical modeling in which preclinical data are integrated with human population PK can facilitate translation of preclinical data to the patient's clinical situation. Moreover, PK/PD modeling and simulations can help in the design of clinical trials aiming to establish optimal dosing regimens to improve patient outcomes. (C) 2020 The Authors. Published by Elsevier B.V.
- Subjects :
- 0301 basic medicine
Microbiology (medical)
Drug
Infectious Medicine
medicine.drug_class
media_common.quotation_subject
030106 microbiology
Antibiotics
Population
Drug Evaluation, Preclinical
Infektionsmedicin
Pharmacology and Toxicology
Bioinformatics
03 medical and health sciences
Mice
0302 clinical medicine
Pharmacokinetics
medicine
Animals
Humans
Pharmacology (medical)
030212 general & internal medicine
Dosing
education
media_common
education.field_of_study
Pharmacokinetics/pharmacodynamics
Bacteria
Dose-Response Relationship, Drug
business.industry
General Medicine
In vitro models
Bacterial Infections
Farmakologi och toxikologi
Animal infection models
Mathematical modeling
Anti-Bacterial Agents
Clinical trial
Disease Models, Animal
Infectious Diseases
Pharmacodynamics
Infection type
Drug Monitoring
business
Subjects
Details
- ISSN :
- 18727913
- Volume :
- 56
- Issue :
- 2
- Database :
- OpenAIRE
- Journal :
- International journal of antimicrobial agents
- Accession number :
- edsair.doi.dedup.....33213d0e6043ff4a05d09a2adf503d98