Towards clinically relevant dose ratios for Cabamiquine and Pyronaridine combination using P. falciparum field isolate data.

ABSTRACT: The selection and combination of dose regimens for antimalarials involve complex considerations including pharmacokinetic and pharmacodynamic interactions. In this study, we use immediate ex vivo P. falciparum field isolates to evaluate the effect of cabamiquine and pyronaridine as standalone treatments and in combination therapy. We feed the data into a pharmacometrics model to generate an interaction map and simulate meaningful clinical dose ratios. We demonstrate that the pharmacometrics model of parasite growth and killing provides a detailed description of parasite kinetics against cabamiquine-susceptible and resistant parasites. Pyronaridine monotherapy provides suboptimal killing rates at doses as high as 720 mg. In contrast, the combination of a single dose of 330 mg cabamiquine an

SUBMITTER: Maiga M 

PROVIDER: S-EPMC11372057 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature