The effect of parenteral nutrition fluids on the binding of therapeutic drugs to human serum in vitro.

The competitive binding of seven therapeutic drugs (carbamazepine, phenytoin, phenobarbital, procainamide, quinidine, theophylline, and valproic acid) to human serum and to five commonly used parenteral nutrition fluids in vitro was studied using equilibrium dialysis. For five of the drugs, all parenteral nutrition fluids bound less drug than human serum-phenobarbital (up to 14% less), phenytoin (up to 46% less), procainamide (up to 43% less), quinidine (up to 25% less), and valproic acid (up to 77% less)-suggesting that the presence of these fluids might increase the free fraction of these drugs in vivo. For carbamazepine, the fluids bound up to 82% more drug, suggesting that the presence of these fluids might decrease the free fraction of this drug in vivo. For theophylline, the fluids produced a minimal (no more than 5%) effect on binding to serum. The administration of parenteral nutrition fluids may significantly alter the free (active) fraction of some therapeutic drugs.