State‐of‐the‐Art Clinical Article: Pharmacokinetic/Pharmacodynamic Parameters: Rationale for Antibacterial Dosing of Mice and Men

Передовая клиническая статья: фармакокинетические/фармакодинамические параметры: обоснование дозирования антибактериальных препаратов у мышей и человека
William A. Craig
1998-01-01

animal infection modelsantibacterial dosing regimensantimicrobial pharmacodynamicspharmacokinetic/pharmacodynamic parameterssusceptibility breakpoints
Investigations over the past 20 years have demonstrated that antibacterials can vary markedly in the time course of antimicrobial activity. These differences in pharmacodynamic activity have implications for optimal dosage regimens. The results of more recent studies suggest that the magnitude of the pharmacokinetic/pharmacodynamic parameters required for efficacy are relatively similar in animal infection models and in human infections. However, there is still much to learn. Additional studies are needed to further correlate pharmacokinetic/pharmacodynamic parameters for many antibacterials with therapeutic efficacy in a variety of animal infection models and in human infections. The potential value of using pharmacokinetic/pharmacodynamic parameters as guides for establishing optimal dosing regimens for new and old drugs and for new emerging pathogens and resistant organisms, for setting susceptibility breakpoints, and for reducing the cost of drug development should make the continuing search for the therapeutic rationale of antibacterial dosing of mice and men worthwhile.
1
Antibacterials differ markedly in the time course of antimicrobial activity, making pharmacodynamic behavior important for selecting optimal dosing regimens.
2
Further research is needed to correlate pharmacokinetic/pharmacodynamic parameters with therapeutic efficacy across diverse antibacterials, animal models, and human infections.
3
Pharmacokinetic/pharmacodynamic parameters may guide dosing optimization, susceptibility breakpoint setting, and reduction of antibacterial drug-development costs.
4
Recent studies indicate that pharmacokinetic/pharmacodynamic exposure targets for efficacy are relatively similar between animal infection models and human infections.
5
The therapeutic rationale for antibacterial dosing remains incomplete, particularly for new pathogens and resistant organisms.

Antibacterial therapy in animal infection models and human infections

Pharmacokinetic/pharmacodynamic determinants of antimicrobial efficacy and their use to optimize antibacterial dosing regimens

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1998-01-01
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William A. Craig
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