Rabbit Renal Proximal Tubule Suspensions as a Model for Nephrotoxicity Evaluation of Native or in situ Metabolized β-Lactam Antibiotics

Rabbit renal proximal tubule suspensions have proved a convenient model for nephrotoxicity studies, particularly for direct nephrotoxins such as Cephaloridin (Olivier et al., 1992). In order to evaluate the ability of this model to metabolize certain drugs to nephrotoxic compounds, we used another B-lactam antibiotic, Imipenem, known to be nephrotoxic through renal metabolism via hydrolysis by dehydropeptidase I (DHP) (Birnbaum et al., 1985). The use of Cilastatin, an inhibitor of this enzyme, should confirm this metabolic pathway.