Animal models in the pharmacokinetic/pharmacodynamic evaluation of antimicrobial agents

被引:83
作者
Zhao, Miao [1 ,2 ,3 ]
Lepak, Alexander J. [3 ]
Andes, David R. [3 ,4 ,5 ]
机构
[1] Fudan Univ, Hua Shan Hosp, Inst Antibiot, Shanghai, Peoples R China
[2] Minist Hlth, Key Lab Clin Pharmacol Antibiot, Shanghai, Peoples R China
[3] Univ Wisconsin, Dept Med, Sch Med & Publ Hlth, Madison, WI 53706 USA
[4] Univ Wisconsin, Dept Med Microbiol & Immunol, Madison, WI 53706 USA
[5] William S Middleton Mem VA Hosp, Madison, WI USA
关键词
Pharmacokinetics; Pharmacodynamics; Animal model; Drug development; RESISTANT STAPHYLOCOCCUS-AUREUS; URINARY-TRACT-INFECTION; IN-VIVO EFFICACY; EPITHELIAL LINING FLUID; TREATING EXPERIMENTAL PERITONITIS; ESCHERICHIA-COLI PYELONEPHRITIS; BETA-LACTAM ANTIBIOTICS; MURINE PNEUMONIA MODEL; HIGH-LEVEL RESISTANCE; PSEUDOMONAS-AERUGINOSA;
D O I
10.1016/j.bmc.2016.11.008
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Animal infection models in the pharmacokineticipharmacodynamic (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. (C) 2016 Elsevier Ltd. All rights reserved.
引用
收藏
页码:6390 / 6400
页数:11
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