EFFECT OF HALOFANTRINE AND ITS DESBUTYL METABOLITE ON LYMPHOCYTE-PROLIFERATION DYNAMICS

Halofantrine hydrochloride (HF), one of the latest antimalarial agents currently undergoing clinical trials, and its active metabolite, N-de sbutplhalofantrine (DHF), were examined for their effects on human and rat lymphocytes. HF has a biphasic concentration-dependent effect on phytohemagglutinin stimulated proliferation of human lymphocytes. Conc entrations lower than 2.25 mu M enhance, while higher concentrations i nhibit proliferation. The IC50 values were 9.4 mu M for HF, 4.5 mu M f or DHF and 14.7 mu M for chloroquine. In human lymphocytes, enhanced p roliferation was not detected for DHF unlike for HF. Combined achievab le plasma concentrations of HF and DHF may sometimes be in the range w here reduced lymphocyte proliferation occurs in vitro when based on si mple additive dynamics. It remains to be confirmed if malarial treatme nt with HF leads to reduced T-cell responsiveness to antigenic challen ges since HF and DHF persist for several days.