Antipyrine and warfarin disposition in a patient with idiopathic hypoalbuminemia

In a subject with the rare condition of idiopathic hypoalbuminemia, antipyrine and warfarin disposition was investigated to determine whether, in an otherwise healthy subject, low albumin concentrations affect the kinetics of these prototypic drugs. Because antipyrine is negligibly bound to albumin its disposition would be expected to be normal, but because at usual therapeutic doses warfarin is 99% bound to albumin, warfarin elimination would be expected to be accelerated in idiopathic hypoalbuminemia. In our patient antipyrine disposition was normal, whereas warfarin clearance was increased and plasma warfarin half-life reduced. The apparent volume of distribution of warfarin was within normal range. Warfarin binding to the patient's plasma was decreased; the free fraction of warfarin in plasma was correspondingly elevated. Albumin isolated from the patient and purified exhibited kinetic values for warfarin binding. Caution is necessary in extending these results to other drugs and other patients with idiopathic hypoalbuminemia since the validity of such extrapolations depends on the extent to which the drug investigated is normally bound to albumin and also on the magnitude of the particular patient's hypoalbuminemia at the precise time of study.