Population pharmacokinetic (PK) models were developed to describe the relationship of ceftazidime and avibactam concentrations in plasma with those in epithelial lining fluid (ELF) in healthy volunteers and to compare ELF concentrations with plasma PK/pharmacodynamic (PD) targets.

The analysis used data from the phase I study which, using non-compartmental calculations, showed that the area under the curve (AUC) of each drug in the ELF is approximately 31–35% of that in plasma. However, non-compartmental AUC methods average across the studied concentration range and therefore do not necessarily calculate penetration at the most clinically relevant concentrations.

In the current compartmental modelling analysis, ELF penetration of both ceftazidime (52%) and avibactam (42%) was greater than previously calculated at plasma concentrations relevant for efficacy (~ 8 mg/l for ceftazidime and ~ 1 mg/l for avibactam), and results suggest ELF exposures of both drugs exceeded levels required for efficacy in plasma.