Considerations regarding PK/PD theory for antibiotics treatment from a pharmacokinetic perspective

Kitamura Yoshiaki

doi:10.2745/dds.33.10

In order to predict the in vivo effects of antibiotic therapy, a pharmacokinetic/pharmacodynamic (PK/PD) index is conventionally selected from three indices, including the ratio of the area under the curve to the minimum inhibitory concentration (AUC/MIC), the ratio of the maximum plasma concentration to the MIC (C_max/MIC), and the period of time for which the drug concentration exceeds the MIC (time above MIC), depending on the in vitro characteristics of the antibiotic. Convention dictates that the in vivo efficacy of a concentration-dependent antibiotic is related to its AUC/MIC and/or C_max/MIC, while that of a time-dependent antibiotic is related to its time above MIC. The “PK/PD index map” proposes the optimal PK/PD index for a given antibiotic based on a mathematical simulation model. This model consists of a PK unit, which is a typical 1-compartment model with a gut compartment, and a PD unit, which is an enhanced-death constant-replication model. The association between the two units was created on the basis that the plasma concentration at a given point in time determines the effect at that time. It was observed that the recommended index provided by the PK/PD index map was generally in good agreement with the conventional classification, providing theoretical support for that classification. The PK/PD index map is a practical guide for optimizing antibiotic therapy and also has the potential to determine the most favorable pharmacokinetic profile for a given antibiotic. Consequently, the PK/PD index map may help to establish a rational goal for the DDS research after the selection of a candidate molecule.

Considerations regarding PK/PD theory for antibiotics treatment from a pharmacokinetic perspective

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