pa-824 and Tuberculosis--Meningeal

Pretomanid is a nitroimidazole antimicrobial active against drug-resistant Mycobacterium tuberculosis and approved in combination with bedaquiline and linezolid (BPaL) to treat multidrug-resistant (MDR) pulmonary tuberculosis (TB). However, the penetration of these antibiotics into the central nervous system (CNS), and the efficacy of the BPaL regimen for TB meningitis, are not well established. Importantly, there is a lack of efficacious treatments for TB meningitis due to MDR strains, resulting in high mortality. We have developed new methods to synthesize

Topics: Animals; Antitubercular Agents; Diarylquinolines; Disease Models, Animal; Humans; Linezolid; Mice; Mycobacterium tuberculosis; Nitroimidazoles; Rabbits; Tuberculosis, Meningeal; Tuberculosis, Multidrug-Resistant

To enhance the drug delivery to the brain with an oil-in-water nanoemulsion of pretomanid via intranasal (IN) administration.. The study involved 70 male Sprague-Dawley rats (160-180 g) that received either 20 mg/kg body weight (b.w.) a nanoemulsion or a 20 mg/kg b.w. of pretomanid in solution via the IN route. The drug was quantified by liquid chromatography-tandem mass spectrometry to investigate whole tissue-drug concentrations, and mass spectrometric imaging to visualize drug localization in the brain.. The results of this study show that IN delivery of oil-in-water nanoemulsion may be very promising for targeting anatomical tuberculosis reservoirs, such as the brain.

Topics: Administration, Intranasal; Animals; Brain; Chromatography, Liquid; Drug Delivery Systems; Emulsions; Male; Nanoparticles; Nitroimidazoles; Rats; Rats, Sprague-Dawley; Solid Phase Extraction; Tuberculosis, Meningeal