Abstract
The action of bacterial endotoxin on the pharmacokinetics of warfarin was investigated in rabbits injected with bacterial endotoxin from E. coli. High doses of endotoxin were able to change the kinetics of warfarin in rabbits by changing its volume of distribution. It is not possible to conclude whether the changes in elimination rate of warfarin in rabbits were mediated through changes in liver blood flow or through impairment of the metabolic capacity of the liver cells.
Keywords: warfarin, endotoxin shock, pharmacokinetics, rabbits, pigs
Sammendrag
Warfarins farmakokinetik blev undersøgt hos kaniner, der fik injektioner af endotoxin (E. coli). Store doser af endotoxin forårsagede chok, og hos kaniner med chok ændredes eliminationen og fordelingen af warfarin. En stor ændring i fordelingsvolumen medførte plasmakoncentrationer, der var højere end begyndelsesværdien. De foreliggende resultater tyder på, at der hos patienter med cirkulationsforstyrrelser induceret af endotoxin kan vrere risiko for toksiske plasmakoncentrationer eller overdosering af lægemidler efter gentagne doseringer.
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Acknowledgment
The technical assistance of Mrs. Gerda Larsen is gratefully appreciated.
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