In Silico Investigation of the Decline in Clinical Efficacy of Artemisinin Combination Therapies Due to Increasing Artemisinin and Partner Drug Resistance.

ABSTRACT: Antimalarial treatment currently relies on an artemisinin derivative and a longer-acting partner drug. With the emergence of resistance to the artemisinin derivatives and the potential pressure this exerts on the partner drugs, the impact of resistance to each drug on efficacy needs to be investigated. An in silico exploration of dihydroartemisinin-piperaquine and mefloquine-artesunate, two artemisinin-based combination therapies that are commonly used in Southeast Asia, was performed. The percentage of treatment failures was simulated from a within-host pharmacokinetic-pharmacodynamic (PKPD) model, assuming that parasites developed increasing levels of (i) artemisinin derivative resistance or (ii) concomitant resistance to both the artemisinin derivative and the partner drug. Because the

SUBMITTER: Zaloumis SG 

PROVIDER: S-EPMC6256805 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature