Chapters authored
Pharmacokinetic and Pharmacodynamic Profiles of Rapid- and Slow-Acting Antimalarial Drugs
Artemisinin and its derivatives are highly effective antimalarial drugs. These compounds combine potent and rapid antimalarial activity with a wide therapeutic index. An initiation of artemisinin resistance, described by a delayed parasite clearance time, is unlikely to cause high-level resistance. Artemisinins as a class demonstrate poor efficacy as monotherapy. This shortcoming can be overcome using oral artemisinin-based combination therapies (ACT) and intravenous-artesunate (IV-AS) in combination with slow-acting partner drugs. Pharmacokinetic and pharmacodynamic (PK/PD) evaluation demonstrates that the rapid efficacy of artemisinins is largely due to drug peak concentrations. Critical evaluation also demonstrates that AS is superior in PK/PD either following oral or intravenous administration when compared to the other rapid-acting artemisinins. This rapid efficacy and decreased mortality demonstrates that currently available artemisinins have a great advantage when combined with slow-acting antimalarial drugs for uncomplicated malaria or in sequential therapy with AS injection initially for severe and complicated malaria. Compared to other ACTs, dihydroartemisinin-piperaquine (DP) demonstrates a superior in PK/PD profile, most likely due to the long half-life of piperaquine. These findings will help us better understand the PK/PD profiles of rapid-acting (artemisinins) and slow-acting (piperaquine) drugs, and suggest how to best use ACTs in the future.
Part of the book: Malaria