Pharmacokinetic Basis for Dose Fractionation in Anti-infective Pharmacology

Dose fractionation (DF) is an experimental method used to identify the pharmacokinetic/pharmacodynamic (PK/PD) index of an anti-bacterial molecule. Two non-compartmental PK parameters Cmax and AUC, in addition to time above a threshold concentration and in vitro potency (e.g.MIC) are the basis for determining the PK/PD index that best describes the pharmacodynamics of the molecule. PK/PD index and magnitude are used to assess the probability of attainment of target through phase 1, 2, 3 clinical trials which ultimately help in defining optimum dose and regimen in patients. The objective of DF is to decrease the correlation between the three PK/PD indices so that the index best associated with efficacy is clearly identified. The requirement of DF is that the molecule should show linear PK in the dose range studied.