Pharmacokinetics-pharmacodynamics of antimicrobial therapy: it's not just for mice anymore

Area of Science:

• Pharmacology
• Infectious Diseases
• Veterinary Medicine

Background:

• Animal infection models have been vital since the 1930s for evaluating antimicrobial chemotherapy.
• These models are fundamental in preclinical assessments of antibacterial agents, guiding dose selection and resistance evaluation.
• Pharmacokinetic-pharmacodynamic (PK-PD) data from animal models are essential for drug development.

Purpose of the Study:

• To highlight the significance of animal infection models in antimicrobial research.
• To emphasize the role of PK-PD data in preclinical drug assessment.
• To discuss the integration of human PK-PD data with animal model findings.

Main Methods:

• Review of historical and current use of animal infection models.
• Analysis of pharmacokinetic-pharmacodynamic (PK-PD) principles in antimicrobial evaluation.
• Examination of recent human PK-PD data in relation to animal model studies.

Main Results:

• Animal PK-PD infection models are indispensable for antibacterial agent assessment, dose selection, and breakpoint determination.
• Extensive human PK-PD data have been generated over the last 15 years for various antimicrobial classes.
• These human data offer a valuable opportunity to corroborate insights derived from animal models.

Conclusions:

• Animal infection models remain a cornerstone in the preclinical evaluation of antimicrobial agents.
• The increasing availability of human PK-PD data allows for validation of animal model findings.
• Integrating both animal and human data enhances the understanding and application of antimicrobial therapies.