Clinical Pharmacology of the Antimalarial Artemisinin-Based Combination and other Artemisinins in Children

Abstract

In 2010, there were estimated 219 million cases of malaria resulting in 666,000 deaths and two-thirds were children. Children are more vulnerable than adults to malaria parasites. In sub-Saharan African countries, maternal malaria is associated with up to 200,000 estimated infant deaths yearly. Malaria is caused by five Plasmodium parasites namely: Plasmodium falciparum, Plasmodium vivax, Plasmodium ovale, Plasmodium malariae, and Plasmodium knowlesi. Of these, Plasmodium falciparum accounts for the majority of the burden of malaria infection in sub-Sahara African countries and is associated with most severe disease. Plasmodium vivax accounts for half of the malarial burden infection in South and East Asia and > 80% of the malarial infections in the America. The artemisinins are very potent and fast-acting antimalarials, inducing more rapid parasite clearance and fever resolution than any other currently used of antimalarial drugs. They are particularly well suited for the treatment of severe Plasmodium falciparum malaria. The standard treatment of malaria infection employs artemisinin-based combination therapy. This antimalarial drug increases treatment efficacy and reduces selection pressure for the emergence of drug resistance. Artemisinins cause a significant reduction of the parasite burden, with a reduction in the parasite population. Only three to four cycles (6 to 8 days) of treatment are required to remove all parasites from the blood. Artemisinins are formulated for oral, intramuscular, intravenous, and rectal routs. Bioavailability after oral dosing is ≤ 30%. The aim of this study is to review the published data on the clinical pharmacology of artemisinins in children.