Model-informed drug development for antimicrobials: translational pharmacokinetic-pharmacodynamic modelling of apramycin to facilitate prediction of efficacious dose in complicated urinary tract infections.

ABSTRACT:

Objectives

The use of mouse models of complicated urinary tract infection (cUTI) has usually been limited to a single timepoint assessment of bacterial burden. Based on longitudinal in vitro and in vivo data, we developed a pharmacokinetic-pharmacodynamic (PKPD) model to assess the efficacy of apramycin, a broad-spectrum aminoglycoside antibiotic, in mouse models of cUTI.

Methods

Two Escherichia coli strains were studied (EN591 and ATCC 700336). Apramycin exposure-effect relationships were established with in vitro time-kill data at pH 6 and pH 7.4 and in mice with cUTI. Immunocompetent mice were treated with apramycin (1.5-30 mg/kg) starting 24 h post-infection. Kidney and bladder tissue were collected 6-96 h post-infection for cfu determination. A PKPD model integrating al

SUBMITTER: Hernandez-Lozano I 

PROVIDER: S-EPMC11695905 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature