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Towards the Clinical Translation of Inhaled Rifampicin for Tuberculosis

Das SC, Khadka P, Sinha S, Katare R, Hill PC, Dummer J.

Respiratory Drug Delivery 2023. Volume , 2023: 11-18.

Abstract:

Tuberculosis (TB) remains a major global health problem. The disease is mainly localized in the lungs but also spreads to other sites. Inhaled therapy is a promising approach to deliver high quantities of anti-TB drugs to the lungs as well as the systemic circulation to achieve desired treatment outcomes sometimes unmet by the current anti-TB regimen that comprises of only oral and injectable drugs. Rifampicin, a potent anti-TB drug, is a promising candidate for inhaled anti-TB therapy and has been widely investigated for its aerosolization potential, toxicity, pharmacokinetics and efficacy against Mycobacterium tuberculosis (Mtb), the causative organism of TB, from the inhaled route. However, there is a the lack of sufficient investigation of safety and pharmacokinetics at a high dose, which is required for TB treatment. To lessen this research gap, we have developed and investigated a drug-only formulation of high-dose inhaled rifampicin for a future clinical trial. Upon in vivo evaluation of safety and pharmacokinetics in laboratory rats following inhaled administration, the powder formulation was found safe to both lungs and liver, and resulted in higher plasma concentrations compared to the oral route. A Phase I clinical trial of the inhaled rifampicin powder is being considered and is hoped to be the first to fulfil the promise of inhaled drugs in anti-TB therapy.