ArticlePLoS neglected tropical diseases2019
Short-course, oral flubendazole does not mediate significant efficacy against Onchocerca adult male worms or Brugia microfilariae in murine infection models.
Article in PLoS neglected tropical diseases, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 1 of them a synthesis that pooled it.
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Who cites it
14 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Preclinical animal models for onchocerciasis and loiasis: A systematic review of applications in drug screening.PLoS neglected tropical diseases · 2026Pooled it
- Onchocerciasis overview: pathogenesis, clinical spectrum, and therapeutic challenges of a neglected tropical disease.Frontiers in parasitology · 2026Review
- Development and validation of small animal models for onchocerciasis and loiasis microfilaricide discovery.PLoS neglected tropical diseases · 2023Article
- The efficacy of the benzimidazoles oxfendazole and flubendazole againstFrontiers in microbiology · 2023Article
- A mouse infection model and long-term lymphatic endothelium co-culture system to evaluate drugs against adult Brugia malayi.PLoS neglected tropical diseases · 2022Article
- NKp46Frontiers in immunology · 2022Article
- Eosinophils in filarial infections: Inducers of protection or pathology?Frontiers in immunology · 2022Review
- Onchocerciasis drug development: from preclinical models to humans.Parasitology research · 2021Review
- Advances in preclinical platforms ofFrontiers in tropical diseases · 2021Article
- Eosinophil-Mediated Immune Control of Adult Filarial Nematode Infection Can Proceed in the Absence of IL-4 Receptor Signaling.Journal of immunology (Baltimore, Md. : 1950) · 2020Article
- Oxfendazole mediates macrofilaricidal efficacy against the filarial nematode Litomosoides sigmodontis in vivo and inhibits Onchocerca spec. motility in vitro.PLoS neglected tropical diseases · 2020Article
- Comparison of immune responses to Loa loa stage-specific antigen extracts in Loa loa-exposed BALB/c mice upon clearance of infection.Parasites & vectors · 2020Article
- Mouse models of Loa loa.Nature communications · 2019Article
- Efficacy of subcutaneous doses and a new oral amorphous solid dispersion formulation of flubendazole on male jirds (Meriones unguiculatus) infected with the filarial nematode Brugia pahangi.PLoS neglected tropical diseases · 2019Article
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22 authors.
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Abstract
The Onchocerca ochengi adult implant and Brugia malayi microfilariemic Severe-Combined Immunodeficient (SCID) mouse models are validated screens to measure macrofilaricidal and microfilaricidal activities of candidate onchocerciasis drugs. The purpose of this study was to assess whether 5 daily sub-cutaneous (s.c.) injections of standard flubendazole (FBZ) suspension (10mg/kg), a single s.c. injection (10mg/kg) or 5 daily repeated oral doses of FBZ amorphous solid dispersion (ASD) formulation (0.2, 1.5 or 15mg/kg) mediated macrofilaricidal efficacy against O. ochengi male worms implanted into SCID mice. The direct microfilaricidal activity against circulating B. malayi microfilariae of single dose FBZ ASD formulation (2 or 40 mg/kg) was also evaluated and compared against the standard microfilaricide, ivermectin (IVM). Systemic exposures of FBZ/FBZ metabolites achieved following dosing were measured by pharmacokinetic (PK) bioanalysis. At necropsy, five weeks following start of FBZ SC injections, there were significant reductions in burdens of motile O. ochengi worms following multiple injections (93%) or single injection (82%). Further, significant proportions of mice dosed following multiple injections (5/6; 83%) or single injection (6/10; 60%) were infection negative (drug-cured). In comparison, no significant reduction in recovery of motile adult O. ochengi adult worms was obtained in any multiple-oral dosage group. Single oral-dosed FBZ did not mediate any significant microfilaricidal activity against circulating B. malayi mf at 2 or 7 days compared with >80% efficacy of single dose IVM. In conclusion, multiple oral FBZ formulation doses, whilst achieving substantial bioavailability, do not emulate the efficacy delivered by the parenteral route in vivo against adult O. ochengi. PK analysis determined FBZ efficacy was related to sustained systemic drug levels rather than achievable Cmax. PK modelling predicted that oral FBZ would have to be given at low dose for up to 5 weeks in the mouse model to achieve a matching efficacious exposure profile.
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