Abstract
The disposition characteristics of warfarin were studied in analbuminemic rats after intravenous bolus injection of 1 and 40 mg/kg of drug to investigate the effects of plasma protein binding on drug disposition. With both doses of warfarin, total body warfarin clearance (CL) was markedly faster and its apparent volume of distribution ( V d β ) significantly greater in the analbuminemic rats in comparison to controls. Further, the apparent elimination rate constant (β) was significantly greater and the corresponding elimination half-life (t 1 2β ) shorter in the rats with low plasma albumin. Whole body autoradiograms demonstrated that the distribution of warfarin to the liver, skeletal muscle and brain was greater in the analbuminemic rats which was in good agreement with the larger V d β observed in this group of rats. The results suggested that the disposition characteristics of warfarin were markedly altered in the rats with low plasma albumin concentrations due to reduced plasma warfarin protein binding.
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