THE RELATION OF THE PLASMA CONCENTRATION OF QUINACRINE TO ITS ANTIMALARIAL ACTIVITY

¹ Department of Pharmacology and Experimental Therapeutics, The Johns Hopkins University

1. Marked variations in the plasma concentration of quinacrine occur in ducks maintained on a constant daily dosage. This variation occurs in individual ducks and in the same duck on different days.

2. There is no correlation between the plasma concentration of quinacrine and its concentration in erythrocytes and tissues either after repeated daily doses or after a single dose. The erythrocyte and tissue concentrations are less variable than the plasma concentrations.

3. Quinacrine is localized in the parasitized erythrocyte. The concentration in the parasitized erythrocytes is less variable than and not correlated with plasma concentrations.

4. Direct experiment indicates that for lophurae malaria in the duck, there is little or no correlation between plasma concentration and therapeutic effect, but good correlation between dosage and therapeutic effect.

5. After administration of a single dose to the duck quinacrine (or total acridines) disappears from the plasma much faster than from the liver. The rate of disappearance of the drug from muscle and erythrocytes is intermediate to that for plasma and liver.

6. The behavior of quinacrine in the duck and the absence of unequivocal evidence to the contrary in man lead us to believe that the situation in man is very similar to that in the duck.