Clofazimine pharmacokinetics in novel rifampicin-resistant tuberculosis regimens: an analysis of the endTB and endTB-Q trials

The study examined the pharmacokinetics of clofazimine, a drug used to treat rifampicin-resistant tuberculosis, in 100 participants from six countries with high disease burden. The median age of participants was 34 years, 32% were female, 18% had diabetes mellitus, and 18% were HIV positive. Clofazimine blood levels were best described by a two-compartment pharmacokinetic model. Co-administration with delamanid increased clofazimine bioavailability by 37%, while HIV infection decreased it by 20%. Diabetes was associated with a 43% reduction in clofazimine clearance. Clofazimine remained in the body with a median of 2.5 years (95th percentile: 0.5 to 8 years) following 9 months of treatment. Researchers recommend further studies to confirm these findings before adjusting clofazimine dosing.