Future In Vitro and Animal Studies: Development of Pharmacokinetic and Pharmacodynamic Efficacy Predictors for Tissue‐Based Antibiotics

For antibiotics to exert their action on bacteria, both the bacteria and the drug need to be in the same place at the same time. The pharmacodynamics of antibiotics, measured as the ratio of area under the concentration-time curve:minimum inhibitory concentration (AUC:MIC), the ratio of plasma concentration:MIC, or time above MIC, indexes the pharmacokinetic properties of an antibiotic (in vivo) to a measure of microbiologic (antimicrobial) activity. Antimicrobial activity is measured as the MIC, and the pharmacokinetics generally used are those in the blood. However, if the infection is not in the blood but in some peripheral tissue such as the lung, it is the concentration of the drug in the lung that the pathogen sees, and thus the concentration in the blood (serum or plasma) is not important. Both in vitro and in vivo studies can aid in the development of pharmacodynamic parameters that characterize the drug-pathogen interaction, resulting in the determination of a dose or dosage regimen capable of curing an infection clinically.