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

Author:

Shin Eunjeong1,Zhang Yongzhen1,Zhou Jieqiang1,Lang Yinzhi1,Sayed Alaa R. M.1,Werkman Carolin1,Jiao Yuanyuan2,Kumaraswamy Monika34,Bulman Zackery P.5ORCID,Luna Brian M.6,Bulitta Jürgen B.1ORCID

Affiliation:

1. Department of Pharmacotherapy and Translational Research, College of Pharmacy, University of Florida, Orlando, Florida, USA

2. Peking University Cancer Hospital, Beijing, China

3. Division of Infectious Diseases and Global Public Health, Department of Medicine, University of California San Diego, La Jolla, California, USA

4. Infectious Diseases Section, VA San Diego Healthcare System, San Diego, California, USA

5. Department of Pharmacy Practice, College of Pharmacy, University of Illinois Chicago, Chicago, Illinois, USA

6. Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, Los Angeles, California, USA

Abstract

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.

Funder

HHS | NIH | National Institute of Allergy and Infectious Diseases

Publisher

American Society for Microbiology

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