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Pharmacokinetics of eight anticoagulant rodenticides in mice after single oral administration
V Vandenbroucke1, A Bousquet-Melou, P De Backer
1Department of Pharmacology, Toxicology, Biochemistry and Organ Physiology, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium. virginie.vandenbroucke@ugent.be
Abstract:
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.
Insights
This study tracked eight rodenticides in mice, finding second-generation anticoagulants persist longer in plasma and liver than first-generation types. This pharmacokinetic data aids in understanding rodenticide poisoning cases.
Area of Science:
- Veterinary Toxicology
- Pharmacokinetics
- Analytical Chemistry
Background:
- Anticoagulant rodenticides are widely used, posing risks of poisoning in animals and humans.
- Understanding the pharmacokinetic profiles of these compounds is crucial for diagnosis and treatment.
- Limited data exists on the comparative pharmacokinetics of various first and second-generation anticoagulant rodenticides.
Purpose of the Study:
- To determine the pharmacokinetic behavior of eight anticoagulant rodenticides in mice.
- To develop and validate an LC-ESI-MS/MS method for rodenticide analysis in plasma and liver.
- To compare the elimination half-lives of first- and second-generation rodenticides.
Main Methods:
- Mice were orally administered one of eight rodenticides at 0.5 LD(50).
- Plasma and liver samples were collected at various time points up to 21 days.
- Rodenticide concentrations were quantified using a validated LC-ESI-MS/MS method.
Main Results:
- Elimination half-lives in plasma were shorter for first-generation (e.g., coumatetralyl: 0.52 days) than second-generation rodenticides (e.g., brodifacoum: 91.7 days).
- Liver elimination half-lives ranged from 15.8 days (coumatetralyl) to 307.4 days (brodifacoum).
- The LC-ESI-MS/MS method demonstrated applicability in a clinical case of suspected rodenticide poisoning in a dog.
Conclusions:
- Second-generation anticoagulant rodenticides exhibit significantly longer elimination half-lives in both plasma and liver compared to first-generation compounds.
- The developed analytical method is suitable for pharmacokinetic studies and clinical diagnostics of rodenticide poisoning.
- These findings provide valuable insights into rodenticide toxicity and persistence.
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