UCSF

Modeling Pyrazinamide Lesion-Specific Pharmacokinetics and Efficacy from Rabbit Data

The Savic Lab is in the process of modeling pyrazinamide’s lesion-specific pharmacokinetics and efficacy based on rabbit data. This will provide a comprehensive lesion-centric model of the disease progression of tuberculosis – accounting for immunopathology and lesion heterogeneity similar to that seen in humans. The sites of mycobacterial infection in tuberculosis patients’ lungs have complex structures and poor vascularization, which obstructs drug distribution to these hard-to-reach-and-treat disease sites, leading to further suboptimal drug concentrations. Our lab has previously modeled drug pharmacokinetics and drug distribution in these difficult-to-treat infections sites using human clinical trial data, but, still, little is known about the exact efficacy levels of drugs in these caseous environments. Our collaborators at the Dartois Lab at Rutgers University have implemented a rabbit model that mimics the human pathology of tuberculosis lesions and eliminates the need for invasive and difficult-to-implement human sample collection.