Importance of Relating Efficacy Measures to Unbound Drug Concentrations for Anti-infective Agents

Overview

Journal Clin Microbiol Rev

Publisher American Society for Microbiology

Specialty Microbiology

Date 2013 Apr 5

PMID 23554417

Citations 61

Authors

Daniel Gonzalez

Stephan Schmidt

Hartmut Derendorf

Affiliations

Soon will be listed here.

Abstract

For the optimization of dosing regimens of anti-infective agents, it is imperative to have a good understanding of pharmacokinetics (PK) and pharmacodynamics (PD). Whenever possible, drug efficacy needs to be related to unbound concentrations at the site of action. For anti-infective drugs, the infection site is typically located outside plasma, and a drug must diffuse through capillary membranes to reach its target. Disease- and drug-related factors can contribute to differential tissue distribution. As a result, the assumption that the plasma concentration of drugs represents a suitable surrogate of tissue concentrations may lead to erroneous conclusions. Quantifying drug exposure in tissues represents an opportunity to relate the pharmacologically active concentrations to an observed pharmacodynamic parameter, such as the MIC. Selection of an appropriate specimen to sample and the advantages and limitations of the available sampling techniques require careful consideration. Ultimately, the goal will be to assess the appropriateness of a drug and dosing regimen for a specific pathogen and infection.

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