Enhancement of the Curative Activity of Primaquine by Concomitant Administration of Mirincamycin

Mirincamycin, a lincomycin derivative with unequivocal but limited activity against the pre-erythrocytic and persisting exoerythrocytic stages of Plasmodium cynomolgi, has been evaluated for capacity to enhance the radical curative potential of the conventional primaquine-chloroquine combination. Established infections with sporozoites of the above plasmodium in rhesus monkeys served this evaluation. The results showed that the dose of primaquine required for cure of 50% of active infections was reduced by one-half to two-thirds by coadministration with 2.5 mg of mirincamycin per kg, 1/16 the 50% curative dose of this lincomycin derivative when used in a mono-drug regimen. The dimensions of the enhancement of the curative activity of primaquine were inversely related to the size of the sporozoite inoculum. The smallest dose of mirincamycin productive of enhancement was 2.5 mg/kg; whether doses larger than 2.5 mg/kg would have been more effective was not determined. There is much to be done before it is known whether a mirincamycin-primaquine combination is useful for suppressive cure or radical cure of the human malarias. Irrespective of that result, the current study serves to focus attention on a somewhat novel approach to the development of more effective and better-tolerated regimens for radical cure, an alternative to the empirical chemical synthesis and screening approach that has dominated searches heretofore.