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

The pharmacokinetics of antipyrine and warfarin were investigated in rabbits with carbon tetrachloride (CCl₄) induced liver damage. The volume of distribution of antipyrine was slightly increased whereas it was markedly reduced for warfarin when estimated 24 h after the CCl₄ injection. Twenty-four h after the CCl₄ injection, the elimination rate constant, the half-life and the body clearance were significantly changed for both compounds. The effect of CCl₄ on the pharmacokinetic parameters of antipyrine persisted 10 days after the CCl₄ injection, whereas the pharmacokinetic parameters of warfarin were normalized at that time. The clinical importance of the changes of drug pharmacokinetics in liver diseases is mentioned, and it is concluded that each drug may behave differently, so that a drug has to be investigated separately in every disease for which the drug is prescribed.