Dehydroemetine

Abstract: Estimates of the global burden range from 50 to 480 million cases per year. 3 Treatment with antibiotics is generally highly effective; however, delays or failures in diagnosis or treatment lead to an estimated 40,000–100,000 deaths per year. Oral metronidazole, a member of the 5-nitroimidazole family, is the standard therapy for treating intestinal amebiasis. Several related compounds, including tinidazole, are efficacious as well. Beyond nitroimidazoles, several alternative drug therapies have been used for invasive amebiasis, including emetine and dehydroemetine, which remain available in the United States for use by patients after failed metronidazole treatment. Chloroquine has also been used for extraintestinal abscess and has shown similar cure rates to metronidazole. 4 More recently, nitazoxanide, a thiazolide derivative with a broad spectrum of activity against anaerobic bacteria and parasites, has also been shown to be an effective treatment in amebic diarrhea. 5 After therapy with metronidazole, there can be a high rate of parasite persistence in the gut, 6 which was recently observed in an outbreak in Japan. 7 Hence, a treatment course with a luminal agent such as iodoquinol is recommended after metronidazole therapy. There have been few comparisons of these drugs in humans. We have developed a mouse model of amebiasis whereby mice develop persistent infection with intestinal inflammation after injection of ameba. In this work, we use this model to examine the comparative efficacy of existing and novel drug compounds.

Abstract: The preparation and physico-chemical characterization of lyophilized polyisohexylcyanoacrylate nanoparticles loaded with dehydroemetine (DHE) for the treatment of visceral leishmaniasis disease is described. The resulting formulation was found to efficiently absorb DHE and gave very reproducible preparations with regard to the size and drug adsorption rate. Stability has been confirmed for at least 24 months. The acute toxicity of DHE was reduced in intravenous administration by its association with nanoparticles. Data concerning tissue distribution in mice showed that DHE nanoparticles were rapidly cleared from the blood stream and that they mainly concentrated in the reticuloendothelial system. Furthermore, DHE linkage to the carrier reduced the cardiac concentrations of the drug.

Abstract: Summary Natural emetine, synthetic 2-dehydroemetine or the corresponding 14C-labeled compounds were injected intraperitoneally into guinea pigs in the form of the dihydrochloride. The unlabeled drugs were determined spectrofluorometrically, and the 14C-labeled compounds by combustion and liquid scintillation counting. These determinations show that: Dehydroemetine is eliminated more rapidly from each individual organ than is emetine. Dehydroemetine disappears relatively more quickly from the heart than from the liver, whereas the reverse is true of emetine. This may in some way be related to the equal therapeutic activity and lower cardiotoxicity of dehydroemetine compared with emetine. After an intraperitoneal injection of 14C-labeled emetine or dehydroemetine, 95% of the injected radioactivity was recovered in the feces while only 5% appeared in the urine.