The integration of pharmacokinetics and pathogen susceptibility data in the design of rational dosing regimens

• Published in: Methods and findings in experimental and clinical pharmacology Vol. 26; no. 10; p. 781
• Main Authors: Maglio, D, Nicolau, D P
• Format: Journal Article
• Language: English
• Published: Spain 01.12.2004
• Subjects: Anti-Infective Agents - pharmacokinetics; Anti-Infective Agents - therapeutic use; Dose-Response Relationship, Drug; Drug Administration Schedule; Humans; Microbial Sensitivity Tests - methods; Microbial Sensitivity Tests - standards
• ISSN: 0379-0355
• DOI: 10.1358/mf.2004.26.10.872560

The integration of pharmacokinetic and pathogen susceptibility data has had an increasing impact on the design of dosage regimens. Pathogen susceptibility is often described by the minimum inhibitory concentration (MIC). While the MIC is an indicator of drug potency, it does not predict pharmacologic response in vivo when drug concentrations are fluctuating. To this end, three pharmacokinetic/pharmacodynamic (PK/PD) parameters that result from indexing pharmacokinetics to MIC have proven quite useful. A number of experimental models of infection have determined the magnitude of each parameter, AUC/MIC, Cmax/MIC and %T>MIC, required for the optimal treatment of specific pathogens. These measurements have proven to be predictive of clinical outcomes as well. As a result, PK/PD breakpoints have been determined based on the likelihood that the pharmacokinetic profile of a given dose will achieve a target PK/PD parameter value. These breakpoints correlate well with treatment success or failure, particularly evident in infections conducive to microbiologic sampling such as otitis media. Therefore, PK/PD assessments have fostered a much more targeted approach to the treatment of patients with infectious diseases, and have proven useful in the selection of antimicrobial therapy and the development of novel dosing strategies.