Activity of oxantel pamoate monotherapy and combination chemotherapy against Trichuris muris and hookworms: revival of an old drug.
Activity of oxantel pamoate monotherapy and combination chemotherapy against Trichuris muris and hookworms: revival of an old drug.
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BACKGROUND: It is widely recognized that only a handful of drugs are available against soil-transmitted helminthiasis, all of which are Eggshell Membrane characterized by a low efficacy against Trichuris trichiura, when administered as single doses.The re-evaluation of old, forgotten drugs is a promising strategy to identify alternative anthelminthic drug candidates or drug combinations.METHODOLOGY: We studied the activity of the veterinary drug oxantel pamoate against Trichuris muris, Ancylostoma ceylanicum and Necator americanus in vitro and in vivo.
In addition, the dose-effect of oxantel pamoate combined with albendazole, mebendazole, levamisole, pyrantel pamoate and ivermectin was studied against T.muris in vitro and additive or synergistic combinations were followed up in vivo.PRINCIPAL FINDINGS: We calculated an ED50 of 4.
7 mg/kg for oxantel pamoate against T.muris in mice.Combinations of oxantel pamoate with pyrantel pamoate behaved antagonistically in vitro (combination index (CI) = 2.
53).Oxantel pamoate combined with levamisole, albendazole or Baritone Ukulele ivermectin using ratios based on their ED50s revealed antagonistic effects in vivo (CI = 1.27, 1.
90 and 1.27, respectively).A highly synergistic effect (CI = 0.
15) was observed when oxantel pamoate-mebendazole was administered to T.muris-infected mice.Oxantel pamoate (10 mg/kg) lacked activity against Ancylostoma ceylanicum and Necator americanus in vivo.
CONCLUSION/SIGNIFICANCE: Our study confirms the excellent trichuricidal properties of oxantel pamoate.Since the drug lacks activity against hookworms it is necessary to combine oxantel pamoate with a partner drug with anti-hookworm properties.Synergistic effects were observed for oxantel pamoate-mebendazole, hence this combination should be studied in more detail.
Since, of the standard drugs, albendazole has the highest efficacy against hookworms, additional investigations on the combination effect of oxantel pamoate-albendazole should be launched.