Inhalable particles containing isoniazid and rifabutin as adjunct therapy for safe, efficacious and relapse-free cure of experimental animal tuberculosis in one month.
Adjunct therapy
Preclinical efficacy
Preclinical safety/tolerability
Pulmonary drug delivery
Journal
Tuberculosis (Edinburgh, Scotland)
ISSN: 1873-281X
Titre abrégé: Tuberculosis (Edinb)
Pays: Scotland
ID NLM: 100971555
Informations de publication
Date de publication:
05 2021
05 2021
Historique:
received:
05
10
2020
revised:
02
03
2021
accepted:
29
03
2021
pubmed:
30
4
2021
medline:
8
1
2022
entrez:
29
4
2021
Statut:
ppublish
Résumé
We investigated the preclinical efficacy and safety/tolerability of biodegradable polymeric particles containing isoniazid (INH) and rifabutin (RFB) dry powder for inhalation (DPI) as an adjunct to oral first-line therapy. Mice and guinea pigs infected with Mycobacterium tuberculosis H37Rv (Mtb) were treated with ∼80 and ∼300 μg of the DPI, respectively, for 3-4 weeks starting 3, 10, and 30 days post-infection. Adjunct combination therapy eliminated culturable Mtb from the lungs and spleens of all but one of 52 animals that received the DPI. Relapse-free cure was not achieved in one mouse that received DPI + oral, human-equivalent doses (HED) of four drugs used in the Directly Observed Treatment, Short Course (DOTS), starting 30 days post-infection. Oral doses (20 mg/Kg/day, each) of INH + RFB reduced Mtb burden from ∼10
Identifiants
pubmed: 33915379
pii: S1472-9792(21)00031-7
doi: 10.1016/j.tube.2021.102081
pii:
doi:
Substances chimiques
Antitubercular Agents
0
Rifabutin
1W306TDA6S
Isoniazid
V83O1VOZ8L
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
102081Informations de copyright
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