The kinetics of triclabendazole disposition in sheep
作者:
D. R. HENNESSY,
E. LACEY,
J. W. STEEL,
R. K. PRICHARD,
期刊:
Journal of Veterinary Pharmacology and Therapeutics
(WILEY Available online 1987)
卷期:
Volume 10,
issue 1
页码: 64-72
ISSN:0140-7783
年代: 1987
DOI:10.1111/j.1365-2885.1987.tb00078.x
出版商: Blackwell Publishing Ltd
数据来源: WILEY
摘要:
Hennessy, D.R., Lacey, E., Steel, J.W.&Prichard, R.K. The kinetics of triclabendazole disposition in sheep. J. vet. Pharmacol. Therap. 10, 64–72.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‐1to 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 (>13 μg 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 μg ml‐′ 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 wa
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