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III. Delineation of the Potentials of Primaquine as a Radical Curative and Prophylactic Drug

This report summarizes the results of experimental studies that underpinned evaluation of primaquine in human volunteers inoculated with sporozoites of the Chesson strain of Plasmodium vivax and current uses of this 8-aminoquinoline for curative and preventive purposes. These experimental studies dealt with both the curative and prophylactic activities of selected 8-aminoquinolines in rhesus monkeys infected or challenged with sporozoites of P. cynomolgi and the toxicities of these agents for non-infected monkeys. They began with preliminary assessments of the curative activities and toxicities of five 6-methoxyquinolines differing from each other with respect to alkyl substituent in the 8-aminoal-kylamino side chain. Primaquine, one of these five derivatives, was the most active and had the best therapeutic index. Results of expanded evaluations of its curative activity and toxicity, compared with results of earlier appraisals of the activities and toxicities of pamaquine, pentaquine, and isopentaquine, indicated that, with respect to therapeutic indexes, prima-quine was superior to these older compounds. Evaluations of primaquine for prophylactic activity followed, with emphasis on the influence of the dosage regimen. Results showed that protection against infection with sporozoites could be attained not only by daily dosage throughout the incubation period, but also by one or two well tolerated doses at appropriate times during this period or by dosage twice weekly for 4 weeks after sporozoite challenge.

^* For present addresses see footnotes, page 612 of this supplement.