Population Pharmacokinetic Analyses for Arbekacin After Administration of ME1100 Inhalation Solution.

The objective of these analyses was to develop a population pharmacokinetic model to describe the arbekacin concentration-time profile in plasma and epithelial lining fluid (ELF) following ME1100 administration. Data were obtained from a post-marketing study for an IV formulation of arbekacin, a Phase 1 study of ME1100 in healthy volunteers, and a Phase 1b study of ME1100 in mechanically ventilated subjects with bacterial pneumonia. Data from the post-marketing study were utilized to develop a population pharmacokinetic model following IV administration and this model was subsequently utilized as the foundation for development of the model characterizing arbekacin disposition following inhalation of ME1100.The final model utilized two-compartments for both plasma and ELF disposition, with movement of arbekacin between the ELF and plasma parameterized using linear first-order rate constants. A bioavailability term was included for the inhalational route of administration, which was estimated to be 19.5% for a typical subject. The model included normalized creatinine clearance (CLcrn) and weight as covariates on arbekacin clearance: CL=(Weight/52.2)0.855•((CLcrn-77)•0.0289+2.32). The model simultaneously described arbekacin concentrations following both IV and inhaled administration and provided acceptable fits to the plasma and ELF data (r2=0.922 and 0.557 for observed vs fitted concentrations, respectively). The developed model will be useful for conducting future analyse...
Source: Antimicrobial Agents and Chemotherapy - Category: Microbiology Authors: Tags: Antimicrob Agents Chemother Source Type: research