Semi-Mechanistic Joint Population Pharmacokinetic Modeling of the Novel Antituberculosis Drug Sorfequiline and Its Metabolite M3 in Healthy Volunteers

Sorfequiline is a novel diarylquinoline in clinical development for the treatment of tuberculosis. In this study, researchers from the University of Cape Town, TB Alliance, Certara, Uppsala University, and Radboud University Medical Center developed the first joint population pharmacokinetic model of sorfequiline and its pharmacologically active metabolite, M3.

Using data from two Phase 1 studies in healthy volunteers, the semi-mechanistic model characterized the pharmacokinetics of both sorfequiline and M3 and quantified the contribution of presystemic metabolism to their exposure. The analysis showed that food substantially reduced presystemic conversion of sorfequiline to M3 and shifted exposure toward the parent drug, supporting fed administration. Model-based simulations also showed that exposures across evaluated dosing regimens remained below established preclinical safety thresholds.

The model provides a quantitative framework for evaluating future drug–drug interaction scenarios, supporting PK/PD analyses, and informing model-based dose optimization as sorfequiline advances in clinical development. Certara scientist David H. Salinger is a co-author of the publication.