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This investigation was undertaken to determine whether eitherd -primaquine orl -primaquine has sufficient advantage over primaquine to warrant evaluation for curative activity in human volunteers infected withPlasmodium vivax . It was found: (i) that the capacities of the isomers and the racemate to cure infections withPlasmodium cynomolgi in rhesus monkeys were essentially identical; (ii) that the subacute toxicities of the isomers and racemate for this monkey were qualitatively the same, but thatl -primaquine was three to five times as toxic asd -primaquine and at least twice as toxic as primaquine; and (iii) that the acute single-dose toxicities of the isomers for mice were not only qualitatively different, but that thed isomer was at least four times as toxic asl -primaquine. Since previous appraisals of curative activity and tolerability of 8-aminoquinolines in rhesus monkeys have correlated well with appraisals in human volunteers, attention was focused on results acquired with these test subjects. The relevant evaluations showed thatd -primaquine had a therapeutic index at least twice that of primaquine. If this advantage carries over to man, problems that now complicate routine use of primaquine might be obviated. Therefore, a critical comparison ofd -primaquine and primaquine in human volunteers seems indicated.

Comparison of the Curative Antimalarial Activities and Toxicities of Primaquine and Its d and l Isomers