Department of Companion Animal Clinical Sciences, Faculty of Veterinary Medicine, Norwegian University of Life Sciences (NMBU), P. O. Box 369, Sentrum, 0102, Oslo, Norway.
Norwegian Poisons Information Centre, Norwegian Institute of Public Health, P. O. Box 222, Skøyen, 0213, Oslo, Norway.
Acta Vet Scand. 2020 Jun 16;62(1):30. doi: 10.1186/s13028-020-00531-5.
Exposure to anticoagulant rodenticides (ARs) in dogs is among the most common causes of poisoning in small animal practice, but information about toxicokinetic of these rodenticides in dogs is lacking. We analysed blood and faeces from five accidentally exposed dogs and 110 healthy dogs by reversed phase ultra-high performance liquid chromatography-tandem mass spectrometry. The aim of the study was to estimate elimination of brodifacoum, bromadiolone and difenacoum after acute exposure, calculate the half-lives of these rodenticides in dogs, estimate faecal elimination in a litter of puppies born, and further to identify the extent of AR exposure in a healthy dog population.
Three dogs were included after single ingestions of brodifacoum; two dogs ingested bromadiolone and one dog ingested difenacoum. Maximum concentrations in faeces were found after day 2-3 for all ARs. The distribution half-lives were 1-10 days for brodifacoum, 1-2 days for bromadiolone and 10 days for difenacoum. Brodifacoum and difenacoum had estimated terminal half-lives of 200-330 days and 190 days, respectively. In contrast, bromadiolone had an estimated terminal half-life of 30 days. No clinical signs of poisoning or coagulopathy were observed in terminal elimination period. In blood, the terminal half-life of brodifacoum was estimated to 8 days. Faeces from a litter of puppies born from one of the poisoned dogs were examined, and measurable concentrations of brodifacoum were detected in all samples for at least 28 days after parturition. A cross-sectional study of 110 healthy domestic dogs was performed to estimate ARs exposure in a dog population. Difenacoum was detected in faeces of one dog. Blood and faecal samples from the remaining dogs were negative for all ARs.
Based on the limited pharmacokinetic data from these dogs, our results suggest that ARs have a biphasic elimination in faeces using a two-compartment elimination kinetics model. We have shown that faecal analysis is suitable and reliable for the assessment of ARs exposure in dogs and a tool for estimating the AR half-lives. Half-lives of ARs could be a valuable indicator in the exposed dogs and provides important information for veterinarians monitoring AR exposure and assessment of treatment length in dogs.
接触抗凝血灭鼠剂（ARs）是小动物临床中最常见的中毒原因之一，但关于这些灭鼠剂在狗体内的毒代动力学信息却很缺乏。我们通过反相超高效液相色谱-串联质谱法分析了 5 只意外接触 ARs 的狗和 110 只健康狗的血液和粪便。本研究的目的是评估急性暴露后 brodifacoum、bromadiolone 和 difenacoum 的消除情况，计算这些灭鼠剂在狗体内的半衰期，估计一窝小狗出生后的粪便排泄量，并进一步确定健康狗群中 AR 暴露的程度。
3 只狗单次摄入 brodifacoum 后被纳入研究；2 只狗摄入 bromadiolone，1 只狗摄入 difenacoum。所有 ARs 的粪便中最大浓度均在第 2-3 天出现。分布半衰期为 1-10 天的 brodifacoum，1-2 天的 bromadiolone 和 10 天的 difenacoum。brodifacoum 和 difenacoum 的估计终末半衰期分别为 200-330 天和 190 天。相比之下，bromadiolone 的估计终末半衰期为 30 天。在终末消除期未观察到中毒或凝血功能障碍的临床症状。在血液中，brodifacoum 的终末半衰期估计为 8 天。从其中一只中毒狗所生的一窝小狗的粪便中进行了检测，在分娩后至少 28 天的所有样本中均检测到了可测量浓度的 brodifacoum。对 110 只健康的家养狗进行了横断面研究，以估计狗群中 ARs 的暴露情况。一只狗的粪便中检测到了 difenacoum。其余狗的血液和粪便样本均未检测到所有 ARs。
基于这些狗的有限药代动力学数据，我们的结果表明，ARs 在粪便中呈双相消除，采用双室消除动力学模型。我们已经证明，粪便分析适用于和可靠用于评估狗的 ARs 暴露，并可作为估计 ARs 半衰期的工具。ARs 的半衰期可以作为暴露狗的一个有价值的指标，为兽医监测 AR 暴露和评估狗的治疗时间长度提供重要信息。
