Distribution of daunorubicin, a potent in vitro trypanocide which lacks in vivo activity, in the blood of trypanosome-infected mice.

Daunorubicin is a highly potent trypanocide in vitro but lacks significant in vivo activity. Distribution in the drug in the blood components and in trypanosomes from mice infected with Trypanosoma rhodesiense was therefore examined. Drug is accumulated in the trypanosomes in a similar manner to, but to a greater extent than, its accumulation in platelets; it is, however, taken up by erythrocytes to a much smaller extent, Drug concentrations in trypanosomes, platelets and erythrocytes declined with its decline in plasma whereas in white blood cells the drug was retained at a constant level. Daunorubicin concentrations in plasma were several orders of magnitude higher than in vitro trypanocidal concentration. Fluorescence microscopy showed that although daunorubicin reaches the trypanosome nucleus, its concentration decreases rapidly so that adequate levels of drug may not be sustained in the bloodstream form of the organism for a sufficient length of time to give a trypanocidal effect in vivo.