Translation of liver stage activity of M5717, a Plasmodium elongation factor 2 inhibitor: from bench to bedside.
Malar J
; 21(1): 151, 2022 May 15.
Article
en En
| MEDLINE
| ID: mdl-35570264
ABSTRACT
BACKGROUND:
Targeting the asymptomatic liver stage of Plasmodium infection through chemoprevention could become a key intervention to reduce malaria-associated incidence and mortality.METHODS:
M5717, a Plasmodium elongation factor 2 inhibitor, was assessed in vitro and in vivo with readily accessible Plasmodium berghei parasites. In an animal refinement, reduction, replacement approach, the in vitro IC99 value was used to feed a Population Pharmacokinetics modelling and simulation approach to determine meaningful effective doses for a subsequent Plasmodium sporozoite-induced volunteer infection study.RESULTS:
Doses of 100 and 200 mg would provide exposures exceeding IC99 in 96 and 100% of the simulated population, respectively.CONCLUSIONS:
This approach has the potential to accelerate the search for new anti-malarials, to reduce the number of healthy volunteers needed in a clinical study and decrease and refine the animal use in the preclinical phase.Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Malaria
/
Antimaláricos
Tipo de estudio:
Prognostic_studies
Límite:
Animals
/
Humans
Idioma:
En
Año:
2022
Tipo del documento:
Article