Prediction of higher ceftazidime-avibactam concentrations in the human renal interstitium compared with unbound plasma using a minimal physiologically based pharmacokinetic model developed in rats and pigs through microdialysis.

ABSTRACT: Last resort antibiotics, like ceftazidime-avibactam (CZA), were used to treat urinary tract infections caused by multidrug-resistant bacteria. However, no data on tissue distribution were available. Our aim was to describe the in vivo kidney distribution of CZA in healthy rats and pigs using a physiologically based pharmacokinetic model (PBPK). Microdialysis probes were inserted into the blood, muscle, and kidney of both species. The experiment started with a retrodialysis by drug period. An i.v. single dose of CZA was administered. Samples were collected for 3 h in rats and 7 h in pigs. A PBPK model was developed to describe tissue and blood CZA pharmacokinetics in animals and to predict human concentrations. The PBPK model adequately described CZA rat and pig data in each tissue a

SUBMITTER: Vallee M 

PROVIDER: S-EPMC11881572 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature