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Both nicotinic acid and salicylic acid undergo glycine conjugation in human beings. Competitive inhibition may therefore be possible when these substances are used concomitantly in patients with hyperlipidemic disorders. The aim of this study was to determine, in six healthy subjects, whether nicotinic acid steady-state levels and total clearance are affected by concomitant aspirin administration. Steady-state nicotinic acid concentrations were obtained in all six volunteers by infusion of nicotinic acid solutions at constant rates (0.075 to 0.100 mg/kg/min) for 6 hours; aspirin (1 gm) was administered orally 120 minutes after the beginning of the infusion of nicotinic acid. Plasma samples were analyzed for nicotinic acid, nicotinuric acid, and salicylic acid. After aspirin administration an immediate marked decrease of nicotinuric acid levels could be observed in all six volunteers, whereas nicotinic acid concentrations increased. We hypothesize that salicylic acid causes a concentration-dependent decrease of total nicotinic acid clearance that results in the saturation (and effective elimination) of the nicotinuric acid conjugation pathway.
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