Integration of pharmacokinetic/pharmacodynamic modeling and simulation in the development of new anti-infective agents - minimum inhibitory concentration versus time-kill curves

被引:19
作者
Schmidt, Stephan [1 ]
Schuck, Edgar [1 ]
Kumar, Vipul [1 ]
Burkhardt, Olaf [1 ,2 ]
Derendorf, Hartmut [1 ]
机构
[1] Univ Florida, Coll Pharm, Dept Pharmaceut, Gainesville, FL 32610 USA
[2] Hannover Med Sch, Dept Pulm Med, D-3000 Hannover, Germany
关键词
EC50; MIC; PK/PD modeling; time-kill curves;
D O I
10.1517/17460441.2.6.849
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
The selection of appropriate doses and dosing regimens is extremely important in antimicrobial therapy in order to increase the chances of clinical success and decrease the likelihood of toxic side effects and the development of resistance. Therefore, empirical treatment of bacterial infections is not reliable enough and more rational approaches are needed. Pharmacokinetic/pharmacodynamic (PK/PD) modeling provides a powerful tool to systematically link PK and PD properties in order to predict antimicrobial efficacy. However, commonly used minimum inhibitory concentration (MIC) based PK/PD indices, although easy to obtain, have a number of limitations. Thus, more reliable PK/PD indices need to be developed. The following article provides an overview of the present PK/PD approaches used in anti-infective therapy and discusses their role in improving drug therapy.
引用
收藏
页码:849 / 860
页数:12
相关论文
共 104 条
[1]   Gatifloxacin and the elderly: pharmacokinetic-pharmacodynamic rationale for a potential age-related dose reduction [J].
Ambrose, PG ;
Bhavnani, SM ;
Cirincione, BB ;
Piedmonte, M ;
Grasela, TH .
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY, 2003, 52 (03) :435-440
[2]   Monte Carlo simulation in the evaluation of susceptibility breakpoints: Predicting the future - Insights from the society of infectious diseases pharmacists [J].
Ambrose, PG .
PHARMACOTHERAPY, 2006, 26 (01) :129-134
[3]   Clinical pharmacodynamics of quinolones [J].
Ambrose, PG ;
Bhavnani, SM ;
Owens, RC .
INFECTIOUS DISEASE CLINICS OF NORTH AMERICA, 2003, 17 (03) :529-+
[4]   The use of Monte Carlo simulation to examine pharmacodynamic variance of drugs:: fluoroquinolone pharmacodynamics against Streptococcus pneumoniae [J].
Ambrose, PG ;
Grasela, DM .
DIAGNOSTIC MICROBIOLOGY AND INFECTIOUS DISEASE, 2000, 38 (03) :151-157
[5]   Pharmacodynamics of the new fluoroquinolone gatifloxacin in murine thigh and lung infection models [J].
Andes, D ;
Craig, WA .
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 2002, 46 (06) :1665-1670
[6]   Pharmacokinetic and pharmacodynamic properties of antimicrobials in the therapy of respiratory tract infections [J].
Andes, D .
CURRENT OPINION IN INFECTIOUS DISEASES, 2001, 14 (02) :165-172
[7]   PROBLEMS IN THERAPEUTIC DRUG-MONITORING - FREE DRUG LEVEL MONITORING [J].
BARRE, J ;
DIDEY, F ;
DELION, F ;
TILLEMENT, JP .
THERAPEUTIC DRUG MONITORING, 1988, 10 (02) :133-143
[8]   Effect of protein binding on the in vitro activity and pharmacodynamics of faropenem [J].
Boswell, FJ ;
Ashby, JP ;
Andrews, JM ;
Wise, R .
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY, 2002, 50 (04) :525-532
[9]  
Box G. E. P., 1979, Robustness in statistics, P201, DOI DOI 10.1016/B978-0-12-438150-6.50018-2
[10]   Pharmacodynamic modeling of ciprofloxacin resistance in Staphylococcus aureus [J].
Campion, JJ ;
McNamara, PJ ;
Evans, MT .
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 2005, 49 (01) :209-219