IN-VIVO DETERMINATIONS OF CARBAMAZEPINE AND CARBAMAZEPINE-10, 11-EPOXIDE BINDING PARAMETERS TO SERUM-PROTEINS IN MONOTHERAPY PATIENTS

The in vivo serum protein binding parameters of carbamazepine (CBZ) an d carbamazepine-10, 11-epoxide (CBZ-E), which was the main metabolite of CBZ in plasma, were determined in sera from 27 patients on CBZ mono therapy. Based on the results by recent studies, the authors assumed t hat CBZ and CBZ-E binding to serum proteins were com-posed of specific binding sites on alpha1-acid glycoprotein (AAG) and albumin. Therefor e, the authors determined the binding parameters of each compound by s pecific binding equation for two proteins. Association constants for d rug-AAG binding were.071 L/mumol for CBZ and.016 L/mumol for CBZ-E. Co nversely, those for drug-albumin binding were.00052 L/mumol for CBZ an d.00072 L/mumol for CBZ-E. Within the investigated total concentration ranges in each compound, the AAG binding contributes largely to the d rug-serum protein interactions. Furthermore, our results indicate that the albumin binding contributes to the nonsaturable serum protein bin ding of these compounds in the therapeutic range.