melarsoprol + eflornithine

Melarsoprol + eflornithine is a combination therapy used for the treatment of second-stage human African trypanosomiasis (HAT), also known as sleeping sickness, particularly in cases caused by Trypanosoma brucei gambiense that have relapsed after standard treatments. Melarsoprol is an arsenic-containing small molecule that acts as a prodrug, metabolized to melarsen oxide, which irreversibly binds to sulfhydryl groups on pyruvate kinase and inhibits trypanothione reductase in the parasite, disrupting energy production and leading to parasite death. Eflornithine is a small molecule inhibitor of ornithine decarboxylase, an enzyme essential for polyamine synthesis in trypanosomes; it exerts its effect by blocking cell division and growth of the parasite. The combination has been studied primarily for relapsing or refractory cases where monotherapy has failed or resistance/tolerance has developed[2][7]. Both drugs are administered intravenously due to poor oral bioavailability.