Plasma disposition and faecal excretion of oxfendazole, fenbendazole and albendazole following oral administration to donkeys.
Abstract: Fenbendazole (FBZ), oxfendazole (fenbendazole sulphoxide, FBZSO), and albendazole (ABZ) were administered orally to donkeys at 10mg/kg bodyweight. Blood and faecal samples were collected from 1 to 120 h post-treatment. The plasma and faecal samples were analysed by high performance liquid chromatography (HPLC). The parent molecule and its sulphoxide and sulphone (FBZSO(2)) metabolites did not reach detectable concentrations in any plasma samples following FBZ administration. ABZ was also not detected in any plasma samples, but its sulphoxide and sulphone metabolites were detected, demonstrating that ABZ was completely metabolised by first-pass mechanisms in donkeys. Maximum plasma concentrations (C(max)) of FBZSO (0.49microg/mL) and FBZSO(2) (0.60microg/mL) were detected at (t(max)) 5.67 and 8.00h, respectively, following administration of FBZSO. The area under the curve (AUC) of the sulphone metabolite (10.33microg h/mL) was significantly higher than that of the parent drug FBZSO (5.17microg h/mL). C(max) of albendazole sulphoxide (ABZSO) (0.08g/mL) and albendazole sulphone (ABZSO(2)) (0.04microg/mL) were obtained at 5.71 and 8.00h, respectively, following ABZ administration. The AUC of the sulphoxide metabolite (0.84microg h/mL) of ABZ was significantly higher than that of the sulphone metabolite (0.50microg h/mL). The highest dry-faecal concentrations of parent molecules were detected at 32, 34 and 30h for FBZSO, FBZ and ABZ, respectively. The sulphide metabolite was significantly higher than the parent molecule after FBZSO administration. The parent molecule was predominant in the faecal samples following FBZ administration. After ABZ administration, the parent molecule was significantly metabolised, probably by gastrointestinal microflora, to its sulphoxide metabolite (ABZSO) that showed a similar excretion profile to the parent molecule in the faecal samples. The AUC of the parent FBZ was significantly higher than that of FBZSO and ABZ in faeces. It is concluded that the plasma concentration of FBZSO was significantly higher than that of FBZ and ABZ. Although ABZ is not licensed for use in Equidae, its metabolites presented a greater plasma kinetic profile than FBZ which is licensed for use in horses. A higher metabolic capacity, first-pass effects and lower absorption of benzimidazoles in donkeys decrease bioavailability and efficacy compared to ruminants.
Publication Date: 2006-06-15 PubMed ID: 16772142DOI: 10.1016/j.tvjl.2005.02.022Google Scholar: Lookup
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- Journal Article
Summary
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The research article investigates the metabolic cycle and excretory patterns of three de-worming agents—Fenbendazole, oxfendazole, and albendazole—in donkeys. After administering the drugs, faecal and plasma samples were analyzed to determine how these medicines metabolize and exit the body. The study reveals that oxfendazole had a higher plasma presence compared to the other two, and that donkeys have lower bioavailability and efficiency with these medications when compared to ruminants.
Study Methodology
- The three de-worming agents Fenbendazole (FBZ), Oxfendazole (FBZSO), and Albendazole (ABZ) were administered to donkeys at a dosage of 10mg/kg body weight.
- Post administration, both blood and faecal samples were taken at periodic intervals from 1 to 120 hours.
- These samples underwent analysis with high-performance liquid chromatography (HPLC) to scrutinize the presence and changes in these de-worming agents and their metabolites.
Plasma Disposition
- Fenbendazole (FBZ) and its metabolites were absent in all blood samples after its administration, which suggests it was not absorbable into the bloodstream.
- Although Albendazole (ABZ) was not detected in the plasma, its metabolites were, indicating that ABZ moves through, and is fully metabolized by, first-pass mechanisms in donkeys.
- After administering FBZSO, top concentrations of FBZSO and FBZSO(2) were found around 5.67 and 8.00 hours respectively.
- Following administration of ABZ, peak levels of the sulphoxide metabolite and sulphone metabolite were noted at approximately 5.71 and 8.00 hours respectively.
- The research points out that there were significantly higher concentrations of these drug’s metabolites than the initial administered drugs.
Faecal Excretion
- The highest dry-faecal concentrations of the administered molecules occurred near the 30-hour mark for all three drugs.
- Following delivery of FBZSO, the sulphide metabolite was significantly higher compared to the parent molecule.
- As per the faecal samples, the parent molecule remained dominant after administering FBZ.
- After administering ABZ, the parent molecule considerably metabolized through the GI microflora to its sulphoxide metabolite.
- The area under the curve, a measure of total drug exposure, for the parent FBZ was higher compared to that for FBZSO and ABZ in faeces.
Conclusions
- The research concluded that the plasma concentration of FBZSO was substantially higher than that of FBZ and ABZ.
- Although ABZ is not licensed for use in equine animals, its metabolites showed a better plasma kinetic profile compared to FBZ, which is permissible for use in horses.
- The study also revealed that due to high metabolic activity, first-pass effects, and lower absorption of these drugs, donkeys experience decreased bioavailability and efficiency when compared to ruminants.
Cite This Article
APA
Gokbulut C, Akar F, McKellar QA.
(2006).
Plasma disposition and faecal excretion of oxfendazole, fenbendazole and albendazole following oral administration to donkeys.
Vet J, 172(1), 166-172.
https://doi.org/10.1016/j.tvjl.2005.02.022 Publication
Researcher Affiliations
- Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, University of Adnan Menderes, Isikli Koyu, Aydin, Turkey. gokbulut40@hotmail.com
MeSH Terms
- Administration, Oral
- Albendazole / pharmacokinetics
- Animals
- Anthelmintics / pharmacokinetics
- Area Under Curve
- Benzimidazoles / pharmacokinetics
- Chromatography, High Pressure Liquid / veterinary
- Equidae
- Feces / chemistry
- Fenbendazole / pharmacokinetics
- Random Allocation
Citations
This article has been cited 5 times.- Ignacio AL, Valentina C, Lucila M, Paula D, Candela C, Carlos L, Laura C. Feeding Management and Albendazole Pharmacokinetics in Pigs. Animals (Basel) 2023 Jan 30;13(3).
- Bach T, Bae S, D'Cunha R, Winokur P, An G. Development and validation of a simple, fast, and sensitive LC/MS/MS method for the quantification of oxfendazole in human plasma and its application to clinical pharmacokinetic study. J Pharm Biomed Anal 2019 Jul 15;171:111-117.
- Prchal L, Podlipná R, Lamka J, Dědková T, Skálová L, Vokřál I, Lecová L, Vaněk T, Szotáková B. Albendazole in environment: faecal concentrations in lambs and impact on lower development stages of helminths and seed germination. Environ Sci Pollut Res Int 2016 Jul;23(13):13015-22.
- Vázquez EM, Romero B, Sahagún AM, López C, Puente R, Rodríguez JM, Fernández N, Diez MJ, Díez R. Analytical Method for the Simultaneous Determination of Albendazole and Metabolites Using HPLC-PDA: A Validation Study. Molecules 2025 May 3;30(9).
- Buono F, Veneziano V, Veronesi F, Molento MB. Horse and donkey parasitology: differences and analogies for a correct diagnostic and management of major helminth infections. Parasitology 2023 Oct;150(12):1119-1138.
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