[A new molecule in antiparasitic therapy: alpha-difluoromethylornithine].
Alpha-difluoromethylornithine (DFMO) is a specific irreversible inhibitor of ornithine-decarboxylase (ODC), key enzyme in the biosynthesis of polyamines, physiological compounds involved in cell multiplication. Pharmacokinetic studies of the drug revealed good oral absorption, low metabolisation and mainly urinary excretion. Short half-life (3 hrs to 3 hrs 30) implicates daily repeated administrations. DFMO is well tolerated, side effects being reversible on discontinuing drug therapy. They chiefly include diarrheas, hematological perturbations (thrombocytopenia) and hear losses (high dosages). Experimental studies show best results on trypanosomes: curative action in mice infected with Trypanosoma brucei brucei. DFMO is effective too against infection with sporozoïtes of Plasmodium berghei. Early clinical observations in African patients with Trypanosoma brucei gambiense sleeping sickness show favorable results: efficacy in both stages of the disease, without significant toxicity. Further trials are required to define optimal therapeutic applications. By the way, DFMO already seems to be a promising alternative to conventional therapy of African trypanosomiasis, expecting other indications in the field of antiparasitic chemotherapy.
D000818:Animals; D004195:Disease Models, Animal; D000518:Eflornithine / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D010271:Parasites / Q000187:drug effects; D010272:Parasitic Diseases / Q000188:drug therapy*; D011073:Polyamines / Q000378:metabolism
D011073:Polyamines; D000518:Eflornithine
Une molécule nouvelle en thérapeutique antiparasitaire: l'alpha-difluorométhylornithine.