Plasma protein carbamylation and decreased acidic drug protein binding in uremia

The effects of in vitro carbamylation of plasma with potassium cyanate on drug-protein binding have been investigated. Potassium cyanate added to samples of normal plasma and incubated for 30 to 150 min induced time-related plasma protein carbamylation. Carbamylation of plasma did not influence quinidine protein binding, but resulted in decreased salicylate binding. The increased free fraction of salicylate in plasma correlated with the degree of carbamylation of plasma proteins (r = 0.99; p less than 0.001). Plasma from patients with chronic renal disease showed varying degrees of plasma protein carbamylation, correlating with the values of free plasma salicylate (r = 0.80; p less than 0.05). Scatchard plots for sulfadiazine binding in plasma from patients with uremia and in normal plasma carbamylated in vitro with potassium cyanate showed changes in the 2 groups when compared with those in normal individuals. If cyanate is produced in vivo from urea in patients with uremia, plasma protein carbamylation may play a role in the decreased plasma protein binding of some acidic drugs.