Qigui Li

By Qigui Li and Mark Hickman

Part of the book: Basic Pharmacokinetic Concepts and Some Clinical Applications

By Qigui Li and Brandon Pybus

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