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High-Performance Liquid Chromatography
Published in Adorjan Aszalos, Modern Analysis of Antibiotics, 2020
Joel J. Kirschbaum, Adorjan Aszalos
Parasitism is almost universal in both animals and humans. It is debilitating and frequently disfiguring or fatal. In Africa alone, 1 million children are estimated to die each year from malaria, with 200 million people thought to be infected with schistosomes. The additional food intake required to maintain an infested organism can be equal to the usual daily intake, a quantity often impossible for some victims to maintain. For these reasons, research is continuing to discover more effective drugs. Anthelmintics, antimalarials, antitrichomoniasis, antitypanosamal, and antiprotozoan drugs are considered in the literature: allopurinal [31,32], berberine [33], cambendazole [34], chloroquine [35–37], ciclobendazole [38], dimetridazole [39], diminazene [40], emetine [41], levamisole [42], ivermectin (avermeetin) [43,44], mebendazole [45,46], mefloquine [47], metronidazole [48–50], ornidazole [51], oxfendazole [52], phenothiazine [53], preziquantel [54], primaquine [55], proquamil [56], pyrentel tartrate [57], pyrimethamine [58], quinine [59,60], salicylhydroxamic acid [61], tetramisole [62], thiabendazole [32,63,64], and tinidazole [65,66]. Figure 2 shows the separation of eight benzimidazoles after injecting 5 μg/ml of each compound [34].
Nitazoxanide
Published in M. Lindsay Grayson, Sara E. Cosgrove, Suzanne M. Crowe, M. Lindsay Grayson, William Hope, James S. McCarthy, John Mills, Johan W. Mouton, David L. Paterson, Kucers’ The Use of Antibiotics, 2017
Nitazoxanide has activity against some cestodes (tapeworms), and was originally developed as a veterinary tapeworm drug (Rossignol and Maisonneuve, 1984). Studies in mice demonstrated that nitazoxanide in combination with albendazole killed the larval stage of Taenia crassiceps, a finding that suggested activity in cysticercosis (Palomares-Alonso et al., 2007). However, Gonzalez et al. found that oral nitazoxanide had no cysticidal efficacy in pigs naturally infected with Taenia solium, as compared with albendazole, oxfendazole, praziquantel, or combined albendazole-praziquantel (Gonzalez et al., 2012).
Triclabendazole for the treatment of human fascioliasis and the threat of treatment failures
Published in Expert Review of Anti-infective Therapy, 2021
Luis Marcos, Vicente Maco, Angelica Terashima
Given the emerging TCBZ resistance in fascioliasis, the MDA campaigns should have to be closely monitored by local governments due to the possibility of reemerging infections in the same areas once control becomes less strict [81]. A first step currently being evaluated by FDA is to assess the safety of TCBZ at a dose of 10 mg/kg 12 h apart for two doses in endemic countries. Although this may be useful for tolerability, it still does not answer the question regarding TCBZ-R cases and the best regimen for these particular cases. In addition, combination of therapies may be another option. The broad-spectrum antihelminthic oxfendazole has shown promising results in animals infected with fascioliasis and it is foreseen in the near future a needed clinical trial in humans will take place.
Moxidectin: an oral treatment for human onchocerciasis
Published in Expert Review of Anti-infective Therapy, 2020
Philip Milton, Jonathan I. D. Hamley, Martin Walker, María-Gloria Basáñez
The anti-Wolbachia consortium (A·WOL) was established to find anti-Wolbachia drugs at least as efficacious as doxycycline but requiring considerably shorter treatment courses and without its contra-indications [91,92]. Other anti-Wolbachia drugs that have been trialed in humans include rifampicin and moxifloxacin [108] (results yet to be published), and minocycline [109]. Other compounds screened by A∙WOL that have shown great promise in pre-clinical development, are high-dose rifampicin [110], rifampicin plus albendazole [111], and an optimized azaquinazoline (AWZ1066S) [112]. Other compounds (in the Drugs for Neglected Diseases initiative (DNDi) filariasis portfolio) [113] include oxfendazole (for which a phase I trial is being planned through the Helminth Elimination Platform (HELP)), emodepside (nearing phase II trial in Ghana for safety, tolerability, and dose/regimen selection), and TylAMacTM (ABBV-4083, developed by A∙WOL in partnership with AbbVie [114]), for which a phase II proof-of-concept trial is being prepared in the DRC [113].
Oxfendazole: a promising agent for the treatment and control of helminth infections in humans
Published in Expert Review of Anti-infective Therapy, 2019
Armando E. Gonzalez, Ellen E. Codd, John Horton, Hector H. Garcia, Robert H. Gilman
The pharmacokinetics, safety, and broad spectrum of activity of oxfendazole have consistently been demonstrated in intestinal helminth infections of animals as well as in tissue dwelling larval cestodes (Taenia solium cysticercosis, echinococcosis, T. hydatigena), trematode (fasciolasis), and filarial infections in a wide range of animal models. Whilst animal models are an indication of potential activity in similar human infections, translating this information into human therapies is a significant challenge since the pharmacokinetics and metabolism are often very different. Thus, with each human infection it will be necessary to conduct specific studies to determine effective doses before moving into larger scale studies to register the product. For example, while OXF has been shown to be very effective in porcine cysticercosis, allowing single-dose treatment, the long half-life of OXF and ability to penetrate the brain parenchyma may not be seen with human infections. Similarly, when considering human intestinal nematode infections, it is not possible to directly associate effective doses in domestic species and it will be necessary to undertake dose ranging studies to determine regimens that are effective against the whole range of intestinal nematodes. One of the challenges is therefore to determine the infecting helminth species most likely to be amenable to treatment and to develop this first as a priority. This will in the longer term provide additional safety data to support further study in other infections.