warfarin and Rodent-Diseases

Resistance to the anticoagulant rodenticide warfarin and an increased vitamin K requirement appear to be pleiotropic effects of the gene Rw2. A comparison of pup mortality in F2 (Rw1Rw2 x Rw1Rw2) and backcross (Rw1Rw2 x Rw1Rw1 or reciprocal) matings of wild brown rats in the laboratory revealed significantly greater losses in the F2 litters at 4-8 weeks of age. Some deaths could be attributed directly to haemorrhage resulting from vitamin K deficiency. A newborn warfarin-resistant rat from an F2 litter showed bleeding from the umbilicus and the anus, and died from internal haemorrhage at 18 weeks of age. Another warfarin-resistant male rat dying at the same age had a grossly enlarged skull.

Topics: Alleles; Animals; Animals, Newborn; Drug Resistance; Female; Male; Mortality; Pregnancy; Rats; Rodent Diseases; Vitamin K Deficiency; Warfarin

The half-lives of warfarin and trimethoprim were significantly longer in mice acutely infected with Bacillus piloformis and in mice which ad clinically recovered from previous experimental infection with the organism. The volume of distribution of trimethoprim but not of warfarin was significantly greater in infected mice than in controls. Body clearances of warfarin was significantly reduced in both disease states. For trimethoprim this parameter was only reduced in the acute state of the disease. The importance of careful control of Tyzzer's disease in laboratory animals for use in pharmacological research is stressed.

Topics: Animals; Bacillus; Bacterial Infections; Liver; Male; Mice; Rodent Diseases; Trimethoprim; Warfarin

Topics: Animals; Blood Coagulation Tests; Drug Resistance; Female; Homozygote; Hybridization, Genetic; Hypoprothrombinemias; Injections, Subcutaneous; Male; Nutritional Requirements; Rats; Rodent Diseases; Vitamin K; Vitamin K Deficiency; Warfarin