Improved characterization of aminoglycoside penetration into human lung epithelial lining fluid via population pharmacokinetics

Antimicrob Agents Chemother. 2024 Feb 7;68(2):e0139323. doi: 10.1128/aac.01393-23. Epub 2024 Jan 3.

Abstract

Aminoglycosides are important treatment options for serious lung infections, but modeling analyses to quantify their human lung epithelial lining fluid (ELF) penetration are lacking. We estimated the extent and rate of penetration for five aminoglycosides via population pharmacokinetics from eight published studies. The area under the curve in ELF vs plasma ranged from 50% to 100% and equilibration half-lives from 0.61 to 5.80 h, indicating extensive system hysteresis. Aminoglycoside ELF peak concentrations were blunted, but overall exposures were moderately high.

Keywords: S-ADAPT; amikacin; arbekacin; gentamicin; lung epithelial lining fluid (ELF); model-based meta-analysis; netilmicin; plazomicin; population pharmacokinetics; tobramycin.

MeSH terms

  • Amikacin
  • Aminoglycosides*
  • Anti-Bacterial Agents* / pharmacokinetics
  • Humans
  • Lung

Substances

  • Aminoglycosides
  • Anti-Bacterial Agents
  • Amikacin