Gokbulut C, Bilgili A, Hanedan B, McKellar Q A
Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine and Research and Development Laboratory, University of Adnan Menderes, Aydin, Turkey.
Vet Parasitol. 2007 Sep 30;148(3-4):279-87. doi: 10.1016/j.vetpar.2007.06.028. Epub 2007 Jul 27.
The plasma disposition of fenbendazole (FBZ), oxfendazole (OFZ) and albendazole (ABZ); and the enantiospecific disposition of OFZ, and ABZSO produced were investigated following an oral administration (50 mg/kg) in dogs. Blood samples were collected from 1 to 120 h post-administration. The plasma samples were analysed by high performance liquid chromatography (HPLC). The plasma concentration of FBZ, OFZ, ABZ and their metabolites were significantly different from each other and depended on the drug administered. The sulphone metabolite (FBZSO2) of FBZ was not detected in any plasma samples and the parent molecule ABZ did not reach quantifiable concentrations following FBZ and ABZ administration, respectively. OFZ and its sulphone metabolite attained a significantly higher plasma concentration and remained much longer in plasma compared with FBZ and ABZ and their respective metabolites. The maximum plasma concentrations (Cmax), area under the concentration time curve (AUC) and mean residence time (MRT) of parent OFZ were more than 30, 68 and 2 times those of FBZ, respectively. The same parameters for ABZSO were also significantly greater than those of FBZSO. The ratio for total AUCs of both the parent drug and the metabolites were 1:42:7 for following FBZ, OFZ and ABZ administration, respectively. The enantiomers were never in racemic proportions and (+) enantiomers of both OFZ and ABZSO were predominant in plasma. The AUC of (+) enantiomers of OFZ and ABZSO was, respectively more than three and seven times larger than that of (-) enantiomers of both molecules. It is concluded that the plasma concentration of OFZ was substantially greater compared with FBZ and ABZ. The data on the pharmacokinetic profile of OFZ presented here may contribute to evaluate its potential as an anthelmintic drug for parasite control in dogs.
研究了犬口服(50mg/kg)芬苯达唑(FBZ)、奥芬达唑(OFZ)和阿苯达唑(ABZ)后的血浆处置情况;以及OFZ和所产生的阿苯达唑亚砜(ABZSO)的对映体特异性处置情况。给药后1至120小时采集血样。血浆样品通过高效液相色谱法(HPLC)进行分析。FBZ、OFZ、ABZ及其代谢物的血浆浓度彼此有显著差异,且取决于所给药的药物。在任何血浆样品中均未检测到FBZ的砜代谢物(FBZSO2),并且分别在给予FBZ和ABZ后,母体分子ABZ未达到可定量的浓度。与FBZ及其代谢物以及ABZ及其代谢物相比,OFZ及其砜代谢物达到了显著更高的血浆浓度,并且在血浆中留存的时间长得多。母体OFZ的最大血浆浓度(Cmax)、浓度-时间曲线下面积(AUC)和平均驻留时间(MRT)分别是FBZ的30倍、68倍和2倍以上。ABZSO的相同参数也显著高于FBZSO。给予FBZ、OFZ和ABZ后,母体药物和代谢物的总AUC之比分别为1:42:7。对映体从未处于外消旋比例,并且OFZ和ABZSO的(+)对映体在血浆中占主导地位。OFZ和ABZSO的(+)对映体的AUC分别比这两种分子的(-)对映体的AUC大三倍和七倍以上。得出的结论是,与FBZ和ABZ相比,OFZ的血浆浓度显著更高。此处呈现的关于OFZ药代动力学特征的数据可能有助于评估其作为犬寄生虫控制驱虫药的潜力。