Future in vitro and animal studies: Development of pharmacokinetic and pharmacodynamic efficacy predictors for tissue-based antibiotics

被引:12
作者
Nightingale, CH
机构
[1] Hartford Hosp, Ctr Anti Infect Res & Dev, Hartford, CT 06102 USA
[2] Univ Connecticut, Storrs, CT USA
来源
PHARMACOTHERAPY | 2005年 / 25卷 / 12期
关键词
pharmacokinetics; pharmacodynamics; efficacy predictors; antibiotics;
D O I
10.1592/phco.2005.25.12part2.146S
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
For antibiotics to exert their action on bacteria, both the bacteria and the drug need to be in the same place at the same time. The pharmacodynamics of antibiotics, measured as the ratio of area under the concentration-time curve:minimum inhibitory concentration (AUC:MIC), the ratio of plasma concentration: MIC, or time above MIC, indexes the pharmacokinetic properties of an antibiotic (in vivo) to a measure of microbiologic (antimicrobial) activity Antimicrobial activity is measured as the MIC, and the pharmacokinetics generally used are those in the blood. However, if the infection is not in the blood but in some peripheral tissue such as the lung, it is the concentration of the drug in the lung that the pathogen sees, and thus the concentration in the blood (serum or plasma) is not important. Both in vitro and in vivo studies can aid in the development of pharmacodynamic parameters that characterize the drug-pathogen interaction, resulting in the determination of a dose or dosage regimen capable of curing an infection clinically.
引用
收藏
页码:146S / 149S
页数:4
相关论文
共 11 条
[1]   Animal model pharmacokinetics and pharmacodynamics: a critical review [J].
Andes, D ;
Craig, WA .
INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS, 2002, 19 (04) :261-268
[2]  
Bearden DT, 1999, INFECT MED, V16, P480
[3]   Predicting efficacy of antiinfectives with pharmacodynamics and Monte Carlo simulation [J].
Bradley, JS ;
Dudley, MN ;
Drusano, GL .
PEDIATRIC INFECTIOUS DISEASE JOURNAL, 2003, 22 (11) :982-992
[4]   A combined in vivo pharmacokinetic-in vitro pharmacodynamic approach to simulate target site pharmacodynamics of antibiotics in humans [J].
Delacher, S ;
Derendorf, H ;
Hollenstein, U ;
Brunner, M ;
Joukhadar, C ;
Hofmann, S ;
Georgopoulos, A ;
Eichler, HG ;
Müller, M .
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY, 2000, 46 (05) :733-739
[5]   Antimicrobial pharmacodynamics: Critical interactions of 'bug and drug' [J].
Drusano, GL .
NATURE REVIEWS MICROBIOLOGY, 2004, 2 (04) :289-300
[6]   Microdialysis -: A novel tool for clinical studies of anti-infective agents [J].
Joukhadar, C ;
Derendorf, H ;
Müller, M .
EUROPEAN JOURNAL OF CLINICAL PHARMACOLOGY, 2001, 57 (03) :211-219
[7]   Rational dosing of antibiotics:: the use of plasma concentrations versus tissue concentrations [J].
Liu, P ;
Müller, M ;
Derendorf, H .
INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS, 2002, 19 (04) :285-290
[8]   Differential efficacy of clarithromycin in lung versus thigh infection models [J].
Maglio, D ;
Capitano, B ;
Banevicius, MA ;
Geng, QM ;
Nightingale, CH ;
Nicolau, DP .
CHEMOTHERAPY, 2004, 50 (02) :63-66
[9]   Impact of pharmacodynamics on dosing of macrolides, azalides, and ketolides [J].
Maglio, D ;
Nicolau, DP ;
Nightingale, CH .
INFECTIOUS DISEASE CLINICS OF NORTH AMERICA, 2003, 17 (03) :563-+
[10]   Impact of pharmacodynamics on breakpoint selection for susceptibility testing [J].
Mouton, JW .
INFECTIOUS DISEASE CLINICS OF NORTH AMERICA, 2003, 17 (03) :579-+