In:
Malaria Journal, Springer Science and Business Media LLC, Vol. 21, No. 1 ( 2022-12)
Abstract:
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 IC 99 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 IC 99 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. Graphical Abstract
Type of Medium:
Online Resource
ISSN:
1475-2875
DOI:
10.1186/s12936-022-04171-0
Language:
English
Publisher:
Springer Science and Business Media LLC
Publication Date:
2022
detail.hit.zdb_id:
2091229-8