Gokbulut Cengiz, Akar Ferda, McKellar Quintin A
Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, University of Adnan Menderes, Isikli Koyu, Aydin, Turkey.
Vet J. 2006 Jul;172(1):166-72. doi: 10.1016/j.tvjl.2005.02.022.
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.
按10mg/kg体重给驴口服芬苯达唑（FBZ）、奥芬达唑（芬苯达唑亚砜，FBZSO）和阿苯达唑（ABZ）。在治疗后1至120小时采集血液和粪便样本。血浆和粪便样本通过高效液相色谱法（HPLC）进行分析。给予FBZ后，任何血浆样本中均未检测到母体分子及其亚砜和砜（FBZSO(2)）代谢物。任何血浆样本中也未检测到ABZ，但其亚砜和砜代谢物被检测到，表明ABZ在驴体内通过首过机制完全代谢。给予FBZSO后，分别在5.67小时和8.00小时检测到FBZSO（0.49μg/mL）和FBZSO(2)（0.60μg/mL）的最大血浆浓度（C(max)）。砜代谢物的曲线下面积（AUC）（10.33μg h/mL）显著高于母体药物FBZSO的曲线下面积（5.17μg h/mL）。给予ABZ后，分别在5.71小时和8.00小时获得阿苯达唑亚砜（ABZSO）（0.08μg/mL）和阿苯达唑砜（ABZSO(2)）（0.04μg/mL）的C(max)。ABZ的亚砜代谢物（0.84μg h/mL）的AUC显著高于砜代谢物（0.50μg h/mL）的AUC。FBZSO、FBZ和ABZ在干粪便中的最高浓度分别在32小时、34小时和30小时检测到。给予FBZSO后，硫化物代谢物显著高于母体分子。给予FBZ后，母体分子在粪便样本中占主导地位。给予ABZ后，母体分子可能通过胃肠道微生物群显著代谢为其亚砜代谢物（ABZSO），该代谢物在粪便样本中的排泄曲线与母体分子相似。粪便中母体FBZ的AUC显著高于FBZSO和ABZ的AUC。得出结论，FBZSO的血浆浓度显著高于FBZ和ABZ。尽管ABZ未被批准用于马科动物，但其代谢物的血浆动力学特征比被批准用于马匹的FBZ更显著。与反刍动物相比，驴体内苯并咪唑类药物更高的代谢能力、首过效应和更低的吸收降低了生物利用度和疗效。
