Improved characterization of aminoglycoside penetration into human lung epithelial lining fluid via population pharmacokinetics
Eunjeong Shin, Yong‐Zhen Zhang, Jieqiang Zhou, Yinzhi Lang, Alaa R. M. Sayed, Carolin Werkman, Yuanyuan Jiao, Monika Kumaraswamy, Zackery P. Bulman, Brian Luna, Jürgen B. Bulitta
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.
Topics & Concepts
AminoglycosidePharmacokineticsPenetration (warfare)PopulationLungAntibioticsPharmacologyAntibacterial agentMedicineChemistryBiologyMicrobiologyInternal medicineMathematicsOperations researchEnvironmental healthPneumonia and Respiratory InfectionsAntibiotics Pharmacokinetics and EfficacyInhalation and Respiratory Drug Delivery