Pharmacokinetic-pharmacodynamic modeling of benznidazole and its antitrypanosomal activity in a murine model of chronic Chagas disease

by Assmus F, Adehin A, Hoglund RM, Fortes Francisco A, Lewis MD, Kelly JM, Charman SA, White KL, Shackleford DM, Escudié F, Chatelain E, Scandale I, Tarning J. PLOS Neglected Tropical Diseases 2025, 19(5): e0012968. doi: 10.1371/journal.pntd.0012968.

Summary: Benznidazole, the standard treatment for Chagas disease, is poorly tolerated and has variable efficacy in chronic infections. To optimize dosing regimens, we need a better understanding of how the plasma exposure of benznidazole relates to its activity against the causative agent, Trypanosoma cruzi. The authors of this manuscript used bioluminescence imaging to monitor T. cruzi infection in mice treated with various benznidazole regimens and developed a model to describe the drug’s pharmacokinetic behaviour in mice. Higher doses were absorbed more slowly, and benznidazole exposure in plasma was strongly linked to the probability of curing the infection. This is the first study to characterize the dose-response relationship for benznidazole in mice using bioluminescence imaging.

The post Pharmacokinetic-pharmacodynamic modeling of benznidazole and its antitrypanosomal activity in a murine model of chronic Chagas disease first appeared on DNDi.