by Assmus F, Adehin A, Hoglund RM, Mowbray CE, Gillon JY, Blesson S, Braillard S, Chatelain E, Scandale I, Tarning J. PLoS Neglected Tropical Diseases 2026;20(4):e0014220. doi:10.1371/journal.pntd.0014220
Summary: DNDI-6148 is a novel drug candidate with potent antiparasitic activity against Trypanosoma cruzi and multiple Leishmania species, as shown in laboratory experiments and preclinical animal studies. The authors of this manuscript analysed data from a recent first-in-human clinical trial to better understand the drug’s pharmacokinetic behaviour after oral dosing. Using a modelling approach, they described the relationship between dose and drug exposure and showed that DNDI-6148 displays non-linear pharmacokinetic behaviour, meaning that drug exposure in plasma does not increase proportionally with dose. By characterizing these relationships, their work provides a quantitative framework to guide dose selection in future clinical trials. These findings represent an important step toward developing an effective and accessible oral treatment for Chagas disease and leishmaniasis.