Bioavailability and Pharmacokinetics of Dihydroartemisinin (DHA) and its Analogs—Mechanistic Studies on its ADME

Malaria is an infectious disease that continues to be linked with considerable morbidity and mortality, and significant social and economic impact in developing countries Malaria is transmitted from person to person by the bite of mosquitoes infected with the protozoan parasite Plasmodium spp . P. falciparum , P. vivax , P. malariae , and P. ovale . Of these, P. falciparum is responsible for over 90% of cases and almost all of the malaria deaths worldwide. This review discusses the epidemiology of malaria, its transmission and clinical manifestations, and the current malaria treatment regimens with emphasis on the artemisinins. Included are the efficacy of the artemisinins and their mechanism of action. Their low bioavailability was linked to extensive metabolism, as well as their chemical instability. Different factors that have permitted the emerging resistance to the artemisinins were showcased, probably as poor-dosing regimen and substandard products in developing countries. Also discussed were the plasmodial genes so far implicated in artemisinin resistance. Lastly, based on the available evidence with regard to bioavailability, metabolism, stability, drug transport, and pharmacokinetics, different approaches were proffered for formulations that will enhance therapeutics efficacy.