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2917099 
Journal Article 
The Effect Of Carbon Tetrachloride (CCl4) Induced Liver Damage On The Volume Of Distribution, The Elimination Half-Life And Body Clearance Of Antipyrine And Warfarin In Rabbits 
Ladefoged, O 
1979 
Yes 
Acta Veterinaria Scandinavica
ISSN: 0044-605X
EISSN: 1751-0147 
NIOSH/00155887 
20 
3 
429-437 
The effects of carbon-tetrachloride (56235) on the pharmacokinetics of antipyrine (60800) and warfarin (81812) were studied in rabbits. Male rabbits were injected intravenously with 100 milligrams per kilogram (mg/kg) antipyrine or 3mg/kg warfarin, followed by 0, 0.2 or 0.4 milliliter (ml)/kg carbon-tetrachloride (56235), injected intraperitoneally. Pharmacokinetic parameters including volume of distribution (Vd), half life, and body clearance (Bc) were determined after injection of warfarin and antipyrine and 24 hours and 10 days after injection with carbon-tetrachloride. Seven of ten rabbits injected with antipyrine plus 0.4ml/kg carbon-tetrachloride died. No rabbits died in the groups given antipyrine plus 0.2ml/kg carbon-tetrachloride or warfarin plus carbon-tetrachloride. In rabbits given antipyrine plus 0.2ml/kg carbon-tetrachloride, the half life of antipyrine was increased from 124 to 407 minutes and Bc was decreased from 3.7 to 1.3ml/minute/kg 24 hours after carbon-tetrachloride. Vd was slightly increased from 0.64 to 0.76 liter/kg. Ten days later, Vd was 0.76 liter/kg, the half life was 168 minutes, and Bc was 3.2ml/minute/kg. In rabbits given warfarin plus 0.4ml/kg carbon-tetrachloride, the average Vd for warfarin was decreased from 0.22 to 0.15 liter/kg 24 hours after carbon-tetrachloride. The half life was increased from 247 to 601 minutes, and Bc was reduced from 0.42 to 0.10ml/minute/kg. The parameters returned to the control values 10 days later. The author concludes that with some drugs, elimination is determined by blood flow to the liver. With other drugs, elimination is limited by the enzyme capacity of liver cells. Carbon-tetrachloride induced liver damage might be a useful model for studying the therapeutic implications of liver disease for veterinary clinic workers.