The long‐term effects of the rodenticide, brodifacoum, on blood coagulation and vitamin K metabolism in rats

Mosterd, J.J.; Thijssen, H. H. W.

doi:10.1111/j.1476-5381.1991.tb12463.x

Cited by 49 publications

(32 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Mosterd and Thijssen (1991) reported that brodifacoum rapidly accumulated in the liver and the liver content on day 30 was not different from day 7 after a single oral dose of 0.2 mg/kg bw to rats, which is well in accordance with our results in mice.…”

Section: Discussionsupporting

confidence: 92%

Pharmacokinetics of eight anticoagulant rodenticides in mice after single oral administration

Vandenbroucke

Bousquet‐mélou

Backer

et al. 2008

Vet Pharm & Therapeutics

129

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionsupporting

confidence: 92%

Pharmacokinetics of eight anticoagulant rodenticides in mice after single oral administration

Vandenbroucke

Bousquet‐mélou

Backer

et al. 2008

Vet Pharm & Therapeutics

129

View full text Add to dashboard Cite

show abstract

“…In the rat at least 70% of the hepatic reductase has to be inhibited before comprising the clotting factor synthesis (Mosterd & Thijssen, 1992). Overcapacity of the vitamin K epoxide reductase probably also exists in man (Mosterd & Thijssen, 1991).…”

Section: Discljssionmentioning

confidence: 99%

Vitamin K metabolism and vitamin K1 status in human liver samples: a search for inter‐individual differences in warfarin sensitivity

Thijssen

Drittij-Reijnders

1993

Br J Haematol

View full text Add to dashboard Cite

Vitamin K-dependent parameters in human liver samples were investigated to find a clue to the inter-individual differences in sensitivity for oral anticoagulants. Vitamin K epoxide reductase and vitamin K-dependent carboxylase activity differed 2-3-fold between the samples. Microsomal warfarin binding correlated significantly with the reductase activity. Microsomal vitamin K epoxide reductase of the different samples showed equal sensitivity for warfarin inhibition, I50 about 0.1 microM. Vitamin K epoxide reductase activity stimulated by NADH/lipoamide and microsomal lipoamide dehydrogenase activity showed higher inter-subject variability than the reductase activity by itself. Liver vitamin K1 levels varied 4-5-fold. Total and liver microsomal vitamin K1 levels were correlated. One of the liver samples was obtained from a donor anticoagulated with phenprocoumon and additionally treated with vitamin K1. High levels of the vitamin and its epoxide were present. Phenprocoumon was essentially irreversibly bound to the microsomes. In general the results confirm inter-individual differences in the hepatic vitamin K-dependent systems; the differences as such were found to be small. However, as the various parameters can work synergistically in the same direction, they may well account for the wide dose range observed in oral anticoagulant therapy.

show abstract

“…It is possible dose is not important above a threshold level adequate to reduce blood clotting. Eason et al (1996) demonstrated that possum blood-clotting time began increasing 2 days after brodifacoum treatment, but was only significantly higher than pretreatment values after 7 days, whereas clotting time peaks within 24 h in rats (Mosterd and Thijssen 1991). If the biochemical response duration (Fig.…”

Section: Discussionmentioning

confidence: 92%

Comparative effects of brodifacoum on rats and possums

Littin¹,

O'Connor²,

Eason³

2000

NZPP

View full text Add to dashboard Cite

The anticoagulant brodifacoum is widely used overseas as a rodenticide, and in New Zealand to control rodents and brushtail possums (Trichosurus vulpecula). The efficacy, behavioural and pathological changes and times to death were compared between Norway rats (Rattus norvegicus) and brushtail possums poisoned with brodifacoum. Caged animals were given brodifacoum in wax or cereal baits, observed for signs of toxicosis and changes in behaviour, then autopsied after death. Brodifacoum caused haemorrhaging and death in both species, and although each showed marked changes in behaviour and pathology, they differed in character, time of onset and duration. Results may be explained in part by species differences in behaviour and half-lives of blood clotting factors.

show abstract

The long‐term effects of the rodenticide, brodifacoum, on blood coagulation and vitamin K metabolism in rats

Cited by 49 publications

References 24 publications

Pharmacokinetics of eight anticoagulant rodenticides in mice after single oral administration

Pharmacokinetics of eight anticoagulant rodenticides in mice after single oral administration

Vitamin K metabolism and vitamin K1 status in human liver samples: a search for inter‐individual differences in warfarin sensitivity

Comparative effects of brodifacoum on rats and possums

Contact Info

Product

Resources

About