Abstract

The important factors which are concerned with the physiological disposition of atabrine have been defined.

The distribution of atabrine in the blood is such that observations on its specific antimalarial action should be related to the concentration of the drug in the plasma and, perhaps, indirectly from this, to its concentration in plasma water. The plasma atabrine concentration achieved after single or serial doses is dominated by the tendency of the organs of the body to localize the material within them and by the slow rate at which the drug is degraded. These characteristics are reflected in the low plasma atabrine concentration which is reached after a single dose of atabrine as well as in the low rate of renal excretion. They also, together with the low excretion rate, are reflected in the slow rate of fall of the plasma atabrine concentration on the termination of therapy and by the progressive accumulation of the drug in the body when serial doses are administered over a period of days or weeks.

The administration of repeated doses eventually results in the attainment of an equilibrium between the amount of drug administered and its localization, degradation and excretion. Thereafter, fairly constant plasma atabrine concentrations are maintained with a continuation of the dosage schedule.

The practical importance of the above factors has been examined by a study of the plasma atabrine concentrations achieved in groups of individuals on various regimes of supressive and definitive therapy.