Photo Credit: Christoph Burgstedt
The following is a summary of “Pharmacokinetic-Pharmacodynamic Evidence From a Phase 3 Trial to Support Flat-Dosing of Rifampicin for Tuberculosis,” published in the March 2024 issue of Infectious Disease by Ngo et al.
A large clinical trial (Study 31/ACTG 5349) investigated optimal rifampicin dosing for drug-susceptible tuberculosis (TB).
Researchers conducted a retrospective study evaluating how different levels of rifampicin exposure impacted treatment success and safety in patients with TB.
They analyzed rifampicin exposure (measured from concentration-time profiles) using population nonlinear mixed-effects models, compared flat-dose vs. weight-banded dosing simulations, and evaluated the effect of rifampicin exposure on treatment success (stable culture conversion at 6 months) and TB-related outcomes (at 9, 12, and 18 months) using Cox proportional hazard models. They also used logistic regression to evaluate safety outcomes.
The results showed that model-derived rifampicin exposure ranged from 4.57 to 140.0 mg·h/L, with a median of 41.8 mg·h/L. Pharmacokinetic simulations indicated that flat-dosed rifampicin offered exposure coverage akin to the weight-banded dose. In exposure-efficacy analysis (n = 680), individuals with rifampicin exposure below the median faced similar risks of stable culture conversion and TB-related unfavorable outcomes compared to those above the median. The exposure-safety analysis (n = 722) found no correlation between higher rifampicin exposure and increased severe adverse events.
Investigators concluded that a flat 600mg daily dose of rifampicin could be a viable alternative to weight-based dosing in the standard 6-month TB treatment, but further research is needed to explore potentially even higher dosages.
Source: academic.oup.com/cid/advance-article/doi/10.1093/cid/ciae119/7625232
