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 predialy sis serum compared to postdialysis serum, In our present study with va lproic acid, we observed an opposite effect, where free valproic acid concentration was higher in postdialysis serum. The increased free val proic acid concentrations in postdialysis sera (15.4-77.4% higher in p ostdialysis 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 u ndialyzed serum. This is probably related to removal of some uremic co mpounds during in vitro dialysis. Treatment of both pre- and postdialy sis sera with activated charcoal corrected the binding deficiency of v alproic acid due to removal of both uremic compounds and free fatty ac ids.