Pharmacodynamics of Antimalarial Agents

Abstract

Antimalarials were among the first, and today are among the most widely used, anti-infective agents. The fundamental pharmacodynamic endpoint for antimalarials is quite simple: elimination of this eukaryotic protozoal pathogen from its host; numerous surrogates for this have been developed. Antimalarial therapy is confounded by several key factors including the coexistence of multiple pharmacologically distinct Plasmodium life cycle forms in the human host; limited resources for discovery, development, and deployment of new drugs; and a high requirement for safety due to the enormous patient population and use for chemoprophylaxis of healthy travelers. Further, for any particular drug, myriad influences impact the pharmacological endpoint, including rapidity of the onset of action, potency, ‘static vs. ‘cidal activity, susceptibility to parasite resistance, immune status of the host, and the suitability of prevailing pharmacokinetics. Classic and recently described pharmacodynamic endpoints in preclinical models are presented, as are new insights into the pharmacokinetic drivers of antimalarial pharmacodynamics. The efficacy and safety of existing drugs are surveyed, and some novel experimental agents are discussed.