Animal models in the pharmacokinetic/pharmacodynamic evaluation of antimicrobial agents
Miao Zhao1, Alexander J Lepak2, David R Andes3
1Institute of Antibiotics Hua-shan Hospital, Fudan University & Key Laboratory of Clinical Pharmacology of Antibiotics, Ministry of Health, China; Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
Abstract:
Animal infection models in the pharmacokinetic/pharmacodynamic (PK/PD) evaluation of antimicrobial therapy serve an important role in preclinical assessments of new antibiotics, dosing optimization for those that are clinically approved, and setting or confirming susceptibility breakpoints. The goal of animal model studies is to mimic the infectious diseases seen in humans to allow for robust PK/PD studies to find the optimal drug exposures that lead to therapeutic success. The PK/PD index and target drug exposures obtained in validated animal infection models are critical components in optimizing dosing regimen design in order to maximize efficacy while minimize the cost and duration of clinical trials. This review outlines the key components in animal infection models which have been used extensively in antibiotic discovery and development including PK/PD analyses.
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