title: Animal models in the pharmacokinetic/pharmacodynamic evaluation of antimicrobial agents.
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.
authors.affiliation: Institute 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.
authors.forename: Miao
authors.initials: M
authors.lastname: Zhao
authors.affiliation: Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
authors.forename: Alexander J
authors.initials: AJ
authors.lastname: Lepak
authors.affiliation: Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA; Department of Medical Microbiology and Immunology, University of Wisconsin, Madison, WI, USA; William S. Middleton Memorial VA Hospital, Madison, WI, USA. Electronic address: dra@medicine.wisc.edu.
authors.forename: David R
authors.initials: DR
authors.lastname: Andes
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects*; D001424:Bacterial Infections / Q000188:drug therapy*; D004195:Disease Models, Animal; D008826:Microbial Sensitivity Tests
chemical_list: D000900:Anti-Bacterial Agents
keywords: Animal model; Drug development; Pharmacodynamics; Pharmacokinetics