CARBAMAZEPINE SALICYLATE INTERACTION IN NORMAL AND UREMIC SERA - REDUCED INTERACTION IN UREMIC SERA

Displacement of phenytoin and valproic acid by salicylate have been de scribed. We studied carbamazepine-salicylate interactions in normal an d uremic sera, which have not been studied. Salicylate caused signific ant displacement of carbamazepine from protein binding, leading to hig her concentrations of free carbamazepine. The concentrations of free c arbamazepine were always significantly higher in uremic sera than in n ormal sera. However, when uremic sera were supplemented with both carb amazepine and salicylate, we observed a much lower displacement of car bamazepine and only a slight increase in free carbamazepine concentrat ion. Treatment of uremic sera with activated charcoal corrected the bi nding deficiency for carbamazepine. Known uremic compounds like hippur ic acid and indoxyl sulphate can only partly explain the observed disp lacement 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.