Pathway of oxfendazole from the host into the worm: Trichuris suis in pigs.
Pathway of oxfendazole from the host into the worm: Trichuris suis in pigs.
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DOI：
10.1016/j.ijpddr.2017.11.002
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发表时间：
2017-12
期刊：
影响因子：
--
通讯作者：
Friis C
中科院分区：
文献类型：
--
作者：
Hansen TVA;Williams AR;Denwood M;Nejsum P;Thamsborg SM;Friis C
众所周知，单次口服剂量的苯并咪唑类对鞭虫属的功效是显著的。在人类和动物中的感染率很低，但目前仍用于防治人类鞭毛虫病的控制方案。然而，苯并咪唑类药物从处理过的宿主到鞭虫的途径仍然未知。由于部分成年鞭虫位于盲肠的细胞内，它们可能在肠内容物和粘膜中暴露于驱虫药物。在这项研究中，奥芬达唑及其代谢产物的途径进行了探索，利用T。猪-猪感染模型，通过在单次口服剂量5 mg/kg奥芬达唑后随时间同时测量蠕虫和盲肠粘膜、盲肠组织、盲肠内容物和猪血浆中的药物浓度。此外，为了与体内研究进行比较，研究了T.在体外孵育后检查SUIS。通过高效液相色谱法对奥芬达唑及其代谢物进行定量。多元线性回归分析表明，在T。猪和血浆中的OFZ浓度，沿着盲肠组织/粘膜中OFZ浓度与T. suis，表明奥芬达唑达到T.猪在从胃肠道吸收后通过血肠细胞途径进入蠕虫。芬苯达唑砜在T. suis受血浆中浓度的影响很大。此外，该代谢物在宿主隔室中药物浓度之间的相关性通常最高。与奥芬达唑相比，该代谢产物的血浆和含量之间的相关性特别高，表明这些隔室之间的药物运动水平较高，可能涉及肝肠循环。在体外试验中，猪鞭虫对OFZ、FBZSO 2和FBZ的积累没有明显的代谢。血浆、组织和粘膜中的OFZ浓度是蠕虫中OFZ水平的主要决定因素。血浆FBZSO 2浓度是T.猪。血-肠细胞途径被认为是OFZ到达T.猪。
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 the possible involvement of the enterohepatic circulation. Trichuris suis accumulate OFZ, FBZSO2 and FBZ without significant metabolism in vitro. OFZ concentrations in plasma, tissue and mucosa are major determinants of OFZ levels in worms. FBZSO2 concentration in plasma is the main determinant of FBZSO2 levels in T. suis. The blood-enterocyte pathway is proposed as the major route for OFZ to reach T. suis.
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影响因子：
3.8
作者：
Hansen TV;Hansen M;Nejsum P;Mejer H;Denwood M;Thamsborg SM
通讯作者：
Thamsborg SM
DOI：
10.1111/j.1365-2885.1993.tb00157.x
发表时间：
1993-06-01
影响因子：
1.3
作者：
HENNESSY, DR;STEEL, JW;PRICHARD, RK
通讯作者：
PRICHARD, RK
影响因子：
3.8
作者：
Diawara A;Halpenny CM;Churcher TS;Mwandawiro C;Kihara J;Kaplan RM;Streit TG;Idaghdour Y;Scott ME;Basáñez MG;Prichard RK
通讯作者：
Prichard RK
DOI：
10.1016/j.ijpddr.2014.03.003
发表时间：
2014-08
影响因子：
4
作者：
Hansen, Tina V. A.;Friis, Christian;Nejsum, Peter;Olsen, Annette;Thamsborg, Stig Milan
通讯作者：
Thamsborg, Stig Milan
影响因子：
2.4
作者：
Alvarez, LI;Saumell, CA;Lanusse, CE
通讯作者：
Lanusse, CE