Work

Pharmacokinetics and physiologically based pharmacokinetic modeling of Mycobacteriophages: Insights into pulmonary distribution and clearance

Year: 2026

Type: dataset

Abstract: Bacteriophage therapy is being explored as an alternate therapeutic approach for treating drug-resistant bacteria, including mycobacteria. However, rational phage dosing remains limited by scarce pharmacokinetic (PK) data and an incomplete understanding of tissue distribution. We performed dose-ranging studies in mice of three therapeutic mycobacteriophages (BPsΔ, ZoeJΔ, Muddy) after intravenous (IV) and intratracheal (IT) administration. All phages behaved similarly. IV dosing produced biphasic kinetics with non-proportional exposure and declining tissue-to-plasma ratios, indicating saturable uptake and elimination. IT delivery yielded monophasic profiles with ∼390-fold higher lung exposure and ∼490-fold lower plasma exposure, supporting inhaled therapy for pulmonary mycobacterial infections. Using BPsΔ data, we developed a mechanistic PBPK model incorporating transcytosis, saturable host clearance, plasma elimination, and lymphatic transport. The model accurately predicted ZoeJΔ and Muddy PK, enabled cross-species extrapolation, and showed that phage morphology influences disposition. This framework advances phage therapy toward model-informed, exposure-guided dose and route selection for multidrug-resistant bacterial infections.

Source: DRYAD

DOI: 10.5061/dryad.wwpzgmt1j