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本文引用的文献

1
Development and Validation of Quantitative Ultraperformance Liquid Chromatography-Tandem Mass Spectrometry Assay for Anticoagulant Rodenticides in Liver.建立和验证用于肝脏中抗凝血杀鼠剂的超高效液相色谱-串联质谱定量分析方法
J Agric Food Chem. 2017 Aug 9;65(31):6682-6691. doi: 10.1021/acs.jafc.7b02280. Epub 2017 Jul 27.
2
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J Vet Diagn Invest. 2015 Jan;27(1):112-6. doi: 10.1177/1040638714559970.
3
Clinical use of the activated partial thromboplastin time and prothrombin time for screening: a review of the literature and current guidelines for testing.活化部分凝血活酶时间和凝血酶原时间在筛查中的临床应用:文献综述及当前检测指南
Clin Lab Med. 2014 Sep;34(3):453-77. doi: 10.1016/j.cll.2014.06.005. Epub 2014 Jul 28.
4
Use of a test for proteins induced by vitamin K absence or antagonism in diagnosis of anticoagulant poisoning in dogs: 325 cases (1987-1997).利用维生素K缺乏或拮抗诱导蛋白检测诊断犬类抗凝血剂中毒:325例病例(1987 - 1997年)
J Am Vet Med Assoc. 2003 Jan 15;222(2):194-8. doi: 10.2460/javma.2003.222.194.
5
Rodenticides.灭鼠药
Vet Clin North Am Small Anim Pract. 2002 Mar;32(2):469-84, viii. doi: 10.1016/s0195-5616(01)00003-1.
6
Comparison of the half-lives and regeneration rates of blood clotting factors II, VII, and X in anticoagulant-resistant and susceptible Norway rats (Rattus norvegicus Berk.).抗凝血抗性和敏感的挪威大鼠(褐家鼠)血液凝固因子II、VII和X的半衰期及再生率比较。
Comp Biochem Physiol C Pharmacol Toxicol Endocrinol. 1999 Mar;122(3):307-16. doi: 10.1016/s0742-8413(98)10128-7.
7
Warfarin withdrawal. Pharmacokinetic-pharmacodynamic considerations.华法林撤药。药代动力学-药效学考量。
Clin Pharmacokinet. 1996 Apr;30(4):300-13. doi: 10.2165/00003088-199630040-00003.
8
Mechanism of diphacinone rodenticide toxicosis in the dog and its therapeutic implications.敌鼠钠灭鼠剂对犬的中毒机制及其治疗意义
Am J Vet Res. 1983 Nov;44(11):2009-17.
9
Clinical signs, laboratory changes and toxicokinetics of brodifacoum in the horse.溴敌隆在马体内的临床体征、实验室变化及毒代动力学
Can J Vet Res. 1991 Jan;55(1):21-7.
10
Mechanism of coumarin action: significance of vitamin K epoxide reductase inhibition.香豆素作用机制:维生素K环氧还原酶抑制的意义
Biochemistry. 1978 Apr 18;17(8):1371-7. doi: 10.1021/bi00601a003.

确定马匹中敌鼠酮的近似最小中毒剂量以及相应的血清、血液和肝脏中敌鼠酮浓度:一项初步研究。

Determining an approximate minimum toxic dosage of diphacinone in horses and corresponding serum, blood, and liver diphacinone concentrations: a pilot study.

作者信息

Romano Megan C, Francis Kyle A, Janes Jennifer G, Poppenga Robert H, Filigenzi Michael S, Stefanovski Darko, Gaskill Cynthia L

机构信息

Department of Veterinary Science, University of Kentucky, Lexington, KY, USA.

California Animal Health and Food Safety Laboratory System, School of Veterinary Medicine, University of California-Davis, Davis, CA, USA.

出版信息

J Vet Diagn Invest. 2022 May;34(3):489-495. doi: 10.1177/10406387221086923. Epub 2022 Apr 2.

DOI:10.1177/10406387221086923
PMID:35369800
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9254070/
Abstract

Poisoning of nontarget species is a major concern with the use of anticoagulant rodenticides (ARs). At postmortem examination, differentiating toxicosis from incidental exposure is sometimes difficult. Clotting profiles cannot be performed on postmortem samples, and clinically significant serum, blood, and liver AR concentrations are not well-established in most species. We chose diphacinone for our study because, at the time, it was the publicly available AR most commonly detected in samples analyzed at the University of Kentucky Veterinary Diagnostic Laboratory. We determined an approximate minimum toxic dosage (MTD) of oral diphacinone in 3 horses and measured corresponding serum, blood, and liver diphacinone concentrations. Diphacinone was administered orally to healthy horses. Prothrombin time (PT), activated partial thromboplastin time (aPTT), and serum and blood diphacinone concentrations were measured daily. At the study endpoint, the horses were euthanized, and diphacinone concentration was measured in each liver lobe. The horse that received 0.2 mg/kg diphacinone developed prolonged (>1.5× baseline) PT and aPTT; the horse that received 0.1 mg/kg did not. This suggests an approximate oral MTD in horses of 0.2 mg/kg diphacinone. Median liver diphacinone concentration at this dosage was 1,780 (range: 1,590-2,000) ppb wet weight. Marginal (model-adjusted) mean diphacinone concentrations of liver lobes were not significantly different from one another ( = NS). Diphacinone was present in similar concentrations in both serum and blood at each time after administration, indicating that both matrices are suitable for detection of diphacinone exposure in horses.

摘要

非靶标物种中毒是使用抗凝血灭鼠剂(ARs)时的一个主要问题。在尸检时,有时很难区分中毒与偶然接触。无法对死后样本进行凝血分析,而且在大多数物种中,临床上具有显著意义的血清、血液和肝脏AR浓度尚未明确。我们选择敌鼠作为研究对象,因为当时它是肯塔基大学兽医诊断实验室分析的样本中最常检测到的市售AR。我们确定了3匹马口服敌鼠的近似最小中毒剂量(MTD),并测量了相应的血清、血液和肝脏敌鼠浓度。给健康马匹口服敌鼠。每天测量凝血酶原时间(PT)、活化部分凝血活酶时间(aPTT)以及血清和血液中的敌鼠浓度。在研究终点,对马匹实施安乐死,并测量每个肝叶中的敌鼠浓度。接受0.2mg/kg敌鼠的马出现PT和aPTT延长(>基线的1.5倍);接受0.1mg/kg的马则未出现。这表明马匹口服敌鼠的近似MTD为0.2mg/kg。此剂量下肝脏敌鼠浓度中位数为湿重1780(范围:1590 - 2000)ppb。肝叶的边缘(模型调整)平均敌鼠浓度彼此之间无显著差异(P = 无显著性差异)。给药后各时间点血清和血液中的敌鼠浓度相似,表明这两种基质都适用于检测马匹是否接触敌鼠。