A Proposal of a Pharmacokinetic/pharmacodynamic (PK/PD) Index Map for Selecting an Optimal PK/PD Index from Conventional Indices (AUC/MIC, C_max/MIC, and TAM) for Antibiotics

Abstract

A pharmacokinetic/pharmacodynamic (PK/PD) analysis is important in antibiotic chemotherapy. Basically, the in vivo efficacy of antibiotics that exert concentration-dependent effects can be predicted using conventional PK/PD indices such as the ratio of the area under the curve to the minimum inhibitory concentration (AUC/MIC) and/or the ratio of the maximum plasma concentration to MIC (C_max/MIC), whereas that of antibiotics with time-dependent effects can be determined using the period of time for which the drug concentration exceeds the MIC (time above MIC [TAM]). However, an optimal PK/PD index remains to be established for some antibiotics. Thus, a PK/PD model which describes the PK profile and effect of an antibiotic was developed, and the results obtained from this model were interpreted to form a PK/PD index map to assess the optimal PK/PD index for the antibiotic. The findings from the map were generally consistent with clinical outcomes even for the antibiotics which proved to be exceptions to the conventional classification. For example, AUC/MIC was an optimal index for azithromycin despite its time-dependent bactericidal activity, and C_max/MIC was a poor index for arbekacin despite its concentration-dependent profile. Thus, the map would be useful for selecting the appropriate PK/PD index for an antibiotic.