Pathway of oxfendazole from the host into the worm: Trichuris suis in pigs

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Standard

Pathway of oxfendazole from the host into the worm : Trichuris suis in pigs. / Hansen, Tina V.A.; Williams, Andrew R.; Denwood, Matthew; Nejsum, Peter; Thamsborg, Stig M.; Friis, Christian.

I: International Journal for Parasitology: Drugs and Drug Resistance, Bind 7, Nr. 3, 2017, s. 416-424.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

Harvard

Hansen, TVA, Williams, AR, Denwood, M, Nejsum, P, Thamsborg, SM & Friis, C 2017, 'Pathway of oxfendazole from the host into the worm: Trichuris suis in pigs', International Journal for Parasitology: Drugs and Drug Resistance, bind 7, nr. 3, s. 416-424. https://doi.org/10.1016/j.ijpddr.2017.11.002

APA

Hansen, T. V. A., Williams, A. R., Denwood, M., Nejsum, P., Thamsborg, S. M., & Friis, C. (2017). Pathway of oxfendazole from the host into the worm: Trichuris suis in pigs. International Journal for Parasitology: Drugs and Drug Resistance, 7(3), 416-424. https://doi.org/10.1016/j.ijpddr.2017.11.002

Vancouver

Hansen TVA, Williams AR, Denwood M, Nejsum P, Thamsborg SM, Friis C. Pathway of oxfendazole from the host into the worm: Trichuris suis in pigs. International Journal for Parasitology: Drugs and Drug Resistance. 2017;7(3):416-424. https://doi.org/10.1016/j.ijpddr.2017.11.002

Author

Hansen, Tina V.A. ; Williams, Andrew R. ; Denwood, Matthew ; Nejsum, Peter ; Thamsborg, Stig M. ; Friis, Christian. / Pathway of oxfendazole from the host into the worm : Trichuris suis in pigs. I: International Journal for Parasitology: Drugs and Drug Resistance. 2017 ; Bind 7, Nr. 3. s. 416-424.

Bibtex

@article{b4883fc5c06b46bb8d12461f951a8ab1,
title = "Pathway of oxfendazole from the host into the worm: Trichuris suis in pigs",
abstract = "It is well known that the efficacy of a single oral dose of benzimidazoles against Trichuris spp. infections in humans and animals is poor, but is currently still used in control programmes against human trichuriasis. However, the route of the benzimidazoles from the treated host to Trichuris remains unknown. As parts of adult Trichuris are situated intracellularly in the caecum, they might be exposed to anthelmintic drugs in the intestinal content as well as the mucosa. In this study, the pathway of oxfendazole and its metabolites was explored using a T. suis-pig infection model, by simultaneously measuring drug concentrations within the worms and the caecal mucosa, caecal tissue, caecal content and plasma of pigs over time after a single oral dose of 5 mg/kg oxfendazole. Additionally, for comparison to the in vivo study, drug uptake and metabolism of oxfendazole by T. suis was examined after in vitro incubation. Oxfendazole and metabolites were quantified by High Performance Liquid Chromatography.Multivariate linear regression analysis showed a strong and highly significant association between OFZ concentrations within T. suis and in plasma, along with a weaker association between OFZ concentrations in caecal tissue/mucosa and T. suis, suggesting that oxfendazole reaches T. suis after absorption from the gastrointestinal tract and enters the worms by the blood-enterocyte pathway. The fenbendazole sulfone level in T. suis was highly affected by the concentrations in plasma. In addition, correlations between drug concentrations in the host compartments, were generally highest for this metabolite. In comparison to oxfendazole, the correlation between plasma and content was particularly high for this metabolite, suggesting a high level of drug movement between these compartments and a possibly involvement of the enterohepatic circulation.",
keywords = "Benzimidazole, Drug efficacy, Drug pathway",
author = "Hansen, {Tina V.A.} and Williams, {Andrew R.} and Matthew Denwood and Peter Nejsum and Thamsborg, {Stig M.} and Christian Friis",
year = "2017",
doi = "10.1016/j.ijpddr.2017.11.002",
language = "English",
volume = "7",
pages = "416--424",
journal = "International Journal for Parasitology: Drugs and Drug Resistance",
issn = "2211-3207",
publisher = "Elsevier",
number = "3",

}

RIS

TY - JOUR

T1 - Pathway of oxfendazole from the host into the worm

T2 - Trichuris suis in pigs

AU - Hansen, Tina V.A.

AU - Williams, Andrew R.

AU - Denwood, Matthew

AU - Nejsum, Peter

AU - Thamsborg, Stig M.

AU - Friis, Christian

PY - 2017

Y1 - 2017

N2 - It is well known that the efficacy of a single oral dose of benzimidazoles against Trichuris spp. infections in humans and animals is poor, but is currently still used in control programmes against human trichuriasis. However, the route of the benzimidazoles from the treated host to Trichuris remains unknown. As parts of adult Trichuris are situated intracellularly in the caecum, they might be exposed to anthelmintic drugs in the intestinal content as well as the mucosa. In this study, the pathway of oxfendazole and its metabolites was explored using a T. suis-pig infection model, by simultaneously measuring drug concentrations within the worms and the caecal mucosa, caecal tissue, caecal content and plasma of pigs over time after a single oral dose of 5 mg/kg oxfendazole. Additionally, for comparison to the in vivo study, drug uptake and metabolism of oxfendazole by T. suis was examined after in vitro incubation. Oxfendazole and metabolites were quantified by High Performance Liquid Chromatography.Multivariate linear regression analysis showed a strong and highly significant association between OFZ concentrations within T. suis and in plasma, along with a weaker association between OFZ concentrations in caecal tissue/mucosa and T. suis, suggesting that oxfendazole reaches T. suis after absorption from the gastrointestinal tract and enters the worms by the blood-enterocyte pathway. The fenbendazole sulfone level in T. suis was highly affected by the concentrations in plasma. In addition, correlations between drug concentrations in the host compartments, were generally highest for this metabolite. In comparison to oxfendazole, the correlation between plasma and content was particularly high for this metabolite, suggesting a high level of drug movement between these compartments and a possibly involvement of the enterohepatic circulation.

AB - It is well known that the efficacy of a single oral dose of benzimidazoles against Trichuris spp. infections in humans and animals is poor, but is currently still used in control programmes against human trichuriasis. However, the route of the benzimidazoles from the treated host to Trichuris remains unknown. As parts of adult Trichuris are situated intracellularly in the caecum, they might be exposed to anthelmintic drugs in the intestinal content as well as the mucosa. In this study, the pathway of oxfendazole and its metabolites was explored using a T. suis-pig infection model, by simultaneously measuring drug concentrations within the worms and the caecal mucosa, caecal tissue, caecal content and plasma of pigs over time after a single oral dose of 5 mg/kg oxfendazole. Additionally, for comparison to the in vivo study, drug uptake and metabolism of oxfendazole by T. suis was examined after in vitro incubation. Oxfendazole and metabolites were quantified by High Performance Liquid Chromatography.Multivariate linear regression analysis showed a strong and highly significant association between OFZ concentrations within T. suis and in plasma, along with a weaker association between OFZ concentrations in caecal tissue/mucosa and T. suis, suggesting that oxfendazole reaches T. suis after absorption from the gastrointestinal tract and enters the worms by the blood-enterocyte pathway. The fenbendazole sulfone level in T. suis was highly affected by the concentrations in plasma. In addition, correlations between drug concentrations in the host compartments, were generally highest for this metabolite. In comparison to oxfendazole, the correlation between plasma and content was particularly high for this metabolite, suggesting a high level of drug movement between these compartments and a possibly involvement of the enterohepatic circulation.

KW - Benzimidazole

KW - Drug efficacy

KW - Drug pathway

U2 - 10.1016/j.ijpddr.2017.11.002

DO - 10.1016/j.ijpddr.2017.11.002

M3 - Journal article

C2 - 29156431

VL - 7

SP - 416

EP - 424

JO - International Journal for Parasitology: Drugs and Drug Resistance

JF - International Journal for Parasitology: Drugs and Drug Resistance

SN - 2211-3207

IS - 3

ER -

ID: 185845994