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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

Virkningen af tetraklorkulstof (CCl4) induceret leverbeskadigelse på fordelingsvolumen, halveringstid og body clearance af antipyrin og warfarin hos kaniner

Acta Veterinaria Scandinavica volume 20, pages 429–437 (1979)Cite this article

Abstract

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.

Sammendrag

Fordelingsvolumen, eliminationskonstant, halveringstid og body clearance for antipyrin og warfarin blev bestemt hos normale kaniner og hos de samme kaniner 24 timer og 10 dage efter injektion af tetra-klorkulstof (GG14) 0,4 ml/kg lgv. eller 0,2 ml/kg Igv. Fordelingsvolu-menet for antipyrin var større hos kaninerne 24 timer efter GC14 injektionen, og ændringen kunne stadig påvises 10 dage efter GG14 injektionen. Warfarins fordelingsvolumen var signifikant mindre hos kaninerne 24 timer efter GG14 injektionen sammenlignet med kontrolværdien, men 10 dage efter GG14 infektionen var fordelingsvolumenet igen normaliseret. Eliminationskon & tanten, halveringstiden og body clearance for både antipyrin og warfarin ændredes signifikant 24 timer efter GG14 injektionen. Kun for antipyrin kunne der påvises ændringer i de tre parametre 10 dage efter injektionen.

Den kliniske betydning af ændringer i lægemidlers farmakokinetik ved leversygdomme påpeges. Mulighederne for at anvende CG14 inducerede leverskader som model ved studier af farmakokinetiske konstanter ved leversygdomme i veterinærmedicinen fremhæves.

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Authors and Affiliations

  1. Department of Pharmacology and Toxicology, Royal Veterinary and Agricultural University, Bülowsvej 13, DK 1870, Copenhagen, Denmark

    Ole Ladefoged

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  1. Ole Ladefoged
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The work was supported by the Danish Agricultural and Veterinary Research Council.

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Ladefoged, O. 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. Acta Vet Scand 20, 429–437 (1979). https://doi.org/10.1186/BF03546604

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Acta Veterinaria Scandinavica

ISSN: 1751-0147