Chloroquine-Resistant Plasmodium falciparum: Difference in the Handling of 14 C-Amodiaquin and 14 C-Chloroquine

Abstract

¹⁴ C-amodiaquin and ¹⁴ C-chloroquine were used to study drug binding by preparations of owl monkey erythrocytes infected either with a chloroquine-susceptible (CS) or with a chloroquine-resistant (CR) strain of P. falciparum . Both of these drugs are derivatives of 4-aminoquinoline, but they differ in their side chains, and there are differences in the way they are handled by preparations of erythrocytes infected with malaria parasites. Although the apparent association constant for the binding of either drug is approximately 10 ⁷ mol ⁻¹ , two to three times more radioactivity was bound from ¹⁴ C-amodiaquin than from ¹⁴ C-chloroquine. Furthermore, there was no apparent difference between CS and CR parasites with respect to ¹⁴ C-amodiaquin binding, whereas erythrocytes infected with CR parasites have a deficiency of ¹⁴ C-chloroquine binding. This difference in the handling of amodiaquin probably accounts for its superiority in the treatment of the owl monkey and of humans infected with CR P. falciparum .