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Chapter: Medical Microbiology: An Introduction to Infectious Diseases: Introduction to Pathogenic Parasites: Pathogenesis and Chemotherapy of Parasitic Diseases

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Eflornithine (Difluoromethylornithine) - Parasites Chemotherapy Drugs

Eflornithine is a specific, enzyme-activated, irreversible inhibitor of ornithine decarboxylase (ODC).

Eflornithine  (Difluoromethylornithine)

Eflornithine is a specific, enzyme-activated, irreversible inhibitor of ornithine decarboxylase (ODC). In mammalian cells, decarboxylation of ornithine by ODC is a mandatory step in the synthesis of polyamines, compounds thought to play critical roles in cell divi-sion and differentiation. Originally developed as an antineoplastic agent, eflornithine proved ineffective in cancer chemotherapy trials. With the discovery that polyamines of Trypanosoma species were also synthesized from ornithine, eflornithine was successfullytested in the treatment of animal trypanosomiasis. Host survival was high and associated with decreases in parasitic polyamines and inhibition of nucleic acid synthesis. In the dosage required to treat trypanosomiasis, mammals tolerated the agent well, presumably because T. brucei is 100 times more sensitive to the effects of eflornithine than are mam-malian cells. Eflornithine appears to be cytostatic and requires an intact host immune sys-tem for maximum effect.


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