Salicylates (NSAID) and cephalosporins presenting the N-methyl-thiotetrazole moiety may reduce the effect of vitamin K1, by inhibition of the vitamin K1 recycling.
Vomiting has been observed in the dog after the 1st and the 2nd injections, administered 12 hours apart at 3 times the recommended dose (15 mg of vitamin K1 per kg of body weight per injection).
Repeating dosing (10 days) at 7 times the recommended dose of a degraded solution (degradation of lecithin into lysolecithin is observed with time during the storage of the product) caused intravascular haemolysis, involving marked anaemia and vomiting.
Vitamin K1 is a cofactor necessary for the synthesis of K-dependent coagulation factors (factors II, VII, IX and X). During this synthesis, vitamin K1 is converted into vitamin K1 hydroquinone (active form of vitamin K1) and then into vitamin K1 epoxide. It is then recycled back into vitamin K1. Antivitamin K rodenticides inhibit the recycling of vitamin K1 epoxide, causing a risk of uncontrolled bleeding through the absence of functional factors II, VII, IX and X synthesis. The supply of vitamin K1 must be sufficiently large to activate hydrogenase enzyme that converts it to its active (hydroquinone) form.
After intravenous administration at 5 mg/kg in the dog, the following pharmacokinetic parameters were obtained:
Cmax = 85.2 µg/ml, AUC = 4246 µg.min./ml, T1/2 = 179.5 min., Cl = 1.15 ml/min., a bioavailability of 100 % and a distribution volume estimated at 4 ×10-4 ml.
One hour after intravenous administration, vitamin K1 is detected in the liver (90% unchanged) before being distributed throughout the body.
Some of the vitamin K1 is eliminated with the bile in the intestinal tract after metabolism in the liver, and some is eliminated in urine (in the form of glucuronoconjugated metabolites).