Hennessy D R, Lacey E, Steel J W, Prichard R K
J Vet Pharmacol Ther. 1987 Mar;10(1):64-72. doi: 10.1111/j.1365-2885.1987.tb00078.x.
To investigate whether the disposition of triclabendazole (TCBZ) and its metabolites in blood or bile influenced its flukicidal potency, TCBZ was administered intraruminally at 10 mg kg-1 to sheep surgically fitted with a permanent re-entrant bile duct cannula. The profiles of TCBZ metabolites in peripheral plasma and bile were determined using high performance liquid chromatography. In plasma, only TCBZ sulphoxide (TCBZ-SO) and TCBZ sulphone were present and reached their maximum concentrations (greater than 13 micrograms ml-1) at 18 and 36 h, respectively, after administration. TCBZ metabolites were specifically bound to plasma albumin, which is believed to exert a major influence on the duration of plasma TCBZ metabolite concentrations and consequent exposure of liver fluke. In bile, the major TCBZ metabolites were hydroxylated in the 4' position and secreted predominantly as sulphate esters with lesser proportions as glucuronide conjugates. The major biliary metabolite was conjugated hydroxy TCBZ-SO which reached a maximum concentration in excess of 40 micrograms ml-1 and contributed almost half the total conjugated metabolites. The major free biliary metabolite was TCBZ-SO. Of the administered TCBZ dose, 9.7% was secreted as free metabolites in bile whereas 35.8% was secreted as conjugated metabolites. Approximately 6.5% of the dose was excreted in urine.
为了研究三氯苯达唑（TCBZ）及其代谢产物在血液或胆汁中的分布是否会影响其杀吸虫效力，给手术安装了永久性再进入胆管插管的绵羊经瘤胃内给予10 mg kg-1的TCBZ。使用高效液相色谱法测定外周血浆和胆汁中TCBZ代谢产物的情况。在血浆中，仅存在TCBZ亚砜（TCBZ-SO）和TCBZ砜，给药后分别在18小时和36小时达到其最大浓度（大于13微克/毫升）。TCBZ代谢产物与血浆白蛋白特异性结合，据信这对血浆TCBZ代谢产物浓度的持续时间以及随后肝吸虫的暴露产生主要影响。在胆汁中，主要的TCBZ代谢产物在4'位被羟基化，主要以硫酸酯形式分泌，以葡萄糖醛酸结合物形式分泌的比例较小。主要的胆汁代谢产物是结合型羟基TCBZ-SO，其最大浓度超过40微克/毫升，几乎占结合型代谢产物总量的一半。主要的游离胆汁代谢产物是TCBZ-SO。在所给予的TCBZ剂量中，9.7%以游离代谢产物形式分泌到胆汁中，而35.8%以结合型代谢产物形式分泌。约6.5%的剂量经尿液排出。
