Preclinical Development of Inhalable d-Cycloserine and Ethionamide To Overcome Pharmacokinetic Interaction and Enhance Efficacy against Mycobacterium tuberculosis.
Antimicrob Agents Chemother
; 63(6)2019 06.
Article
en En
| MEDLINE
| ID: mdl-30962335
ABSTRACT
We compared the pharmacokinetics and efficacy of a combination of d-cycloserine (DCS) and ethionamide (ETO) via oral and inhalation routes in mice. The plasma half-life (t1/2) of oral ETO at a human-equivalent dose decreased from 4.63 ± 0.61 h to 1.64 ± 0.40 h when DCS was coadministered. The area under the concentration-time curve from 0 h to time t (AUC0-t ) was reduced to one-third. Inhalation overcame the interaction. Inhalation, but not oral doses, reduced the lung CFU/g of Mycobacterium tuberculosis H37Rv from 6 to 3 log10 in 4 weeks, indicating bactericidal activity.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Tuberculosis Pulmonar
/
Cicloserina
/
Etionamida
/
Mycobacterium tuberculosis
/
Antituberculosos
Límite:
Animals
Idioma:
En
Revista:
Antimicrob Agents Chemother
Año:
2019
Tipo del documento:
Article
País de afiliación:
India