ABSTRACT
Introduction
Tuberculosis (TB) is a global health problem that poses a challenge to global treatment programs. Rifampicin is a potent and highly effective drug for TB treatment; however, higher oral doses than the standard dose (10 mg/kg/day) rifampicin may offer better efficacy in TB treatment.
Areas covered
High oral dose rifampicin is not implemented in anti-TB regimens yet and requires about a 3-fold increase in dose for increased efficacy. We discuss inhaled delivery of rifampicin as an alternative or adjunct to oral high-dose rifampicin. Clinical results of safety, tolerability, and patient compliance with antibiotic dry powder inhalers are reviewed.
Expert opinion
Clinical trials suggest that an approximately 3-fold increase in the standard oral dose of rifampicin may be required for better clinical outcomes. On the other hand, animal studies suggest that inhaled rifampicin can deliver a high concentration of the drug to the lungs and achieve approximately double the plasma concentration than that from oral rifampicin. Clinical trials on inhaled antibiotics suggest that dry powder inhalation is a patient-friendly and well-tolerated approach in treating respiratory infections compared to conventional treatments. Rifampicin, a well-known anti-TB drug given orally, is a good candidate for clinical development as a dry powder inhaler.
Article highlights
The current standard dose of oral rifampicin is not optimal for treatment of tuberculosis and higher oral doses have showed promising results in clinical trials.
Higher oral doses of rifampicin, although promising in reducing treatment duration, have not been implemented in TB treatment regimens.
Pulmonary delivery of rifampicin can be an adjunct or an alternative to oral standard rifampicin, and has the potential to achieve the goals of oral high-dose rifampicin with a smaller dose and possibly less systemic toxicity.
A review of clinical studies on inhaled antibiotic dry powder formulations discusses the safety, tolerability and patient adherence of inhaled antibiotic therapy and the potential of inhaled rifampicin against TB.
Abbreviations
AUC | = | Area under the plasma concentration-time curve |
Cmax | = | Maximum plasma concentration |
CF | = | Cystic fibrosis |
COPD | = | Chronic Obstructive Pulmonary Disease |
DPI | = | Dry powder inhaler |
FEV1 | = | Forced expiratory volume in 1 sec |
HIV | = | Human immunodeficiency virus |
HV | = | Healthy volunteer |
MDR-TB | = | Multidrug resistant TB |
MIC | = | Minimum inhibitory concentration |
MRSA | = | Methicillin resistant Staphylococcus aureus |
Mtb | = | Mycobacterium tuberculosis |
NCFB | = | Non-Cystic Fibrosis Bronchiectasis |
NOAEL | = | No observed adverse effect level |
PK/PD | = | Pharmacokinetics/Pharmacodynamics |
Tmax | = | Time to Cmax |
TB | = | TuberculosisXDR-TB: Extremely drug resistant TB |
WHO | = | World Health Organization |
Declaration of interest
The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.
Reviewer disclosures
Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.