Chemotherapy has often been described in terms of a triangle of two-way reactions involving host, parasite, and drug. Workers in tropical medicine have given considerable attention to the interactions of parasite and host and to the interplays between therapeutic agent and parasite. Mindful of safety, they have also given due consideration to the impact of the drug on the host. The reverse phase of this reaction, the effect of the host on the drug, has received far less attention despite the fact that it, as much as any and more than most reactions, determines therapeutic success or failure. It is this aspect of pharmacology, relating to the physiological disposition and metabolic fate of chemotherapeutic agents, which I would like to discuss in this the Twenty-first Lecture in honor of Charles Franklin Craig.
In developing this subject, I would like to give brief attention to those compounds which are used in the treatment and suppression of malaria, examining the extent to which present day usage is dictated by what the host does to a drug with respect to absorption, plasma binding, tissue localization, excretion, and metabolism.