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) and carbamazepine-10, 11-epoxide (CBZ-E), which was the main metabolite of CBZ in plasma, were determined in sera from 27 patients on CBZ monotherapy. Based on the results by recent studies, the authors assumed that CBZ and CBZ-E binding to serum proteins were composed of specific binding sites on alpha 1-acid glycoprotein (AAG) and albumin. Therefore, the authors determined the binding parameters of each compound by specific binding equation for two proteins. Association constants for drug-AAG binding were .071 L/mumol for CBZ and .016 L/mumol for CBZ-E. Conversely, those for drug-albumin binding were .00052 L/mumol for CBZ and .00072 L/mumol for CBZ-E. Within the investigated total concentration ranges in each compound, the AAG binding contributes largely to the drug-serum protein interactions. Furthermore, our results indicate that the albumin binding contributes to the nonsaturable serum protein binding of these compounds in the therapeutic range.