Inhaled Pyrazinoic Acid Esters for the Treatment of Tuberculosis.
Pharm Res
; 33(10): 2495-505, 2016 10.
Article
in En
| MEDLINE
| ID: mdl-27351427
ABSTRACT
PURPOSE:
Analog development of existing drugs and direct drug delivery to the lungs by inhalation as treatments for multiple and extensively drug resistant (MDR and XDR) tuberculosis (TB) represent new therapeutic strategies. Pyrazinamide (PZA) is critical to drug sensitive TB therapy and is included in regimens for MDR TB. However, PZA-resistant Mycobacterium tuberculosis (Mtb) strains threaten its use. Pyrazinoic acid esters (PAEs) are PZA analogs effective against Mtb in vitro, including against the most common PZA resistant strains. However, PAEs require testing for TB efficacy in animal models.METHODS:
PAEs were delivered daily as aqueous dispersions from a vibrating mesh nebulizer to Mtb infected guinea pigs for 4 weeks in a regimen including orally administered first-line TB drugs.RESULTS:
PAEs tested as a supplement to oral therapy significantly reduced the organ bacterial burden in comparison to infected, untreated control animals. Thus, PAE aerosol therapy is a potentially significant addition to the regimen for PZA resistant MDR-TB and XDR-TB treatment. Interestingly, low dose oral PZA treatment combined with standard therapy also reduced bacterial burden. This observation may be important for PZA susceptible disease treatment.CONCLUSION:
The present study justifies further evaluation of PZA analogs and their lung delivery to treat TB.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Pyrazinamide
/
Tuberculosis, Multidrug-Resistant
/
Mycobacterium tuberculosis
/
Antitubercular Agents
Limits:
Animals
Language:
En
Journal:
Pharm Res
Year:
2016
Type:
Article
Affiliation country:
United States