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-desbutylhalofantrine (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. Concentrations lower than 2.25 microM enhance, while higher concentrations inhibit proliferation. The IC50 values were 9.4 microM for HF, 4.5 microM for DHF and 14.7 microM for chloroquine. In human lymphocytes, enhanced proliferation was not detected for DHF unlike for HF. Combined achievable plasma concentrations of HF and DHF may sometimes be in the range where reduced lymphocyte proliferation occurs in vitro when based on simple additive dynamics. It remains to be confirmed if malarial treatment with HF leads to reduced T-cell responsiveness to antigenic challenges since HF and DHF persist for several days.
Fasanmade
A A
AA
Department of Pharmaceutics, School of Pharmacy, State University of New York at Buffalo 14260, USA.
Jusko
W J
WJ
D000328:Adult; D000704:Analysis of Variance; D000818:Animals; D000962:Antimalarials / Q000378:metabolism / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002738:Chloroquine / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D008214:Lymphocytes / Q000166:cytology / Q000187:drug effects*; D008297:Male; D010616:Phenanthrenes / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000962:Antimalarials; D010616:Phenanthrenes; C044961:1,3-dichloro-6-trifluoromethyl-9-phenanthryl-3-(n-butyl)aminopropanol; D002738:Chloroquine; C023768:halofantrine