Carbamazepine-salicylate interaction in normal and uremic sera: reduced interaction in uremic sera

Displacement of phenytoin and valproic acid by salicylate have been described. We studied carbamazepine-salicylate interactions in normal and uremic sera, which have not been studied. Salicylate caused significant displacement of carbamazepine from protein binding, leading to higher concentrations of free carbamazepine. The concentrations of free carbamazepine were always significantly higher in uremic sera than in normal sera. However, when uremic sera were supplemented with both carbamazepine and salicylate, we observed a much lower displacement of carbamazepine and only a slight increase in free carbamazepine concentration. Treatment of uremic sera with activated charcoal corrected the binding deficiency for carbamazepine. Known uremic compounds like hippuric acid and indoxyl sulphate can only partly explain the observed displacement of carbamazepine in uremic sera. We conclude that salicylate displaces carbamazepine from protein binding in normal sera, but this interaction is significantly reduced in uremic sera.