Can Rifapentine Shorten Treatment Duration for Pulmonary TB?

Maximal treatment efficacy for pulmonary tuberculosis (TB) is likely achieved with 1200 mg rifapentine daily, according to a recent study. However, some patients may be less responsive to the treatment, including men, blacks, patients co-infected with human immunodeficiency virus (HIV), patients who fast during treatment, and patients with large lung cavities.

Rifapentine is a highly active anti-TB antibiotic with the potential to shorten the duration of treatment. However, exposure-response relations and the dose needed for maximal bactericidal activity are unknown.
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In their study, the researchers evaluated the pharmacokinetic and pharmacodynamic data of 657 adult patients with pulmonary TB. They compared 405 patients receiving rifapentine with 252 patients receiving rifampin as part of intensive-phase therapy.

Population pharmacokinetic and pharmacodynamic analyses were conducted with nonlinear mixed-effects modeling. Additionally, time to stable culture conversion of sputum to negative was determined in cultures that were collected over 4 months of therapy.

Results indicated that maximal treatment efficacy for pulmonary TB was likely achieved at 1200 mg daily. However, the researchers also found that exposure to rifapentine was lower in patients who were men, black, had an HIV co-infection, or were fasting while taking the drug. The researchers also found that rifapentine exposure, large lung cavity size, and geographic region were independently associated with time to culture conversion in liquid media.

“Pharmacokinetic/pharmacodynamic results supported level rifapentine dosing in adults and further evaluation of rifapentine at high daily doses as a TB treatment-shortening strategy,” the researchers concluded.

—Christina Vogt

Reference:

Savic RM, Weiner M, MacKenzie WR, et al; Tuberculosis Trials Consortium of the Centers for Disease Control and Prevention. Defining the optimal dose of rifapentine for pulmonary tuberculosis: exposure-response relations from two phase II clinical trials. Clin Pharmacol Ther. 2017;102:321-331. doi:10.1002/cpt.634.