Diminished protein binding capacity of uremic sera for valproate following hemodialysis: role of free fatty acids and uremic compounds.

We previously reported higher free phenytoin concentration in predialysis serum compared to postdialysis serum. In our present study with valproic acid, we observed an opposite effect, where free valproic acid concentration was higher in postdialysis serum. The increased free valproic acid concentrations in postdialysis sera (15.4-77.4% higher in postdialysis sera) were probably related to a 2-to 4-fold increase in free fatty acid concentrations in postdialysis sera. On the other hand, when an aliquot of predialysis serum pool was subjected to in vitro equilibrium dialysis and then both undialyzed and dialyzed serum pools were supplemented with valproic acid and incubated, the concentration of valproic acid in dialyzed serum was significantly lower than the undialyzed serum. This is probably related to removal of some uremic compounds during in vitro dialysis. Treatment of both pre- and postdialysis sera with activated charcoal corrected the binding deficiency of valproic acid due to removal of both uremic compounds and free fatty acids.