Pharmacokinetics of eight anticoagulant rodenticides in mice after single oral administration

布罗迪法库姆 灭鼠剂 抗凝剂 药代动力学 药理学 华法林 医学 口服 毒理 内科学 生物 心房颤动
作者
Virginie Vandenbroucke,Alain Bousquet‐mélou,Julie De Backer,Siska Croubels
出处
期刊:Journal of Veterinary Pharmacology and Therapeutics [Wiley]
卷期号:31 (5): 437-445 被引量:145
标识
DOI:10.1111/j.1365-2885.2008.00979.x
摘要

The first aim of the study was to investigate the pharmacokinetics of eight anticoagulant rodenticides (brodifacoum, bromadiolone, chlorophacinone, coumatetralyl, difenacoum, difethialone, flocoumafen and warfarin) in plasma and liver of the mouse after single oral administration. Eight groups of mice dosed orally with a different anticoagulant rodenticide in a dose equal to one‐half the lethal dose 50 (LD 50 ), were killed at various times up to 21 days after administration. The eight anticoagulant rodenticides were assayed in plasma and liver by an LC‐ESI‐MS/MS method. Depending on the compound, the limit of quantification was set at 1 or 5 ng/mL in plasma. In liver, the limit of quantification was set at 250 ng/g for coumatetralyl and warfarin and at 100 ng/g for the other compounds. The elimination half‐lives in plasma for first‐generation rodenticides were shorter than those for second‐generation rodenticides. Coumatetralyl, a first‐generation product, had a plasma elimination half‐life of 0.52 days. Brodifacoum, a second‐generation product, showed a plasma elimination half‐life of 91.7 days. The elimination half‐lives in liver varied from 15.8 days for coumatetralyl to 307.4 days for brodifacoum. The second aim of the study was to illustrate the applicability of the developed method in a clinical case of a dog suspected of rodenticide poisoning.
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