In vivo binding characteristics of carbamazepine and carbamazepine 10, 11-epoxide to serum proteins in monotherapy adult patients.

The in vivo serum protein binding characteristics of carbamazepine and carbamazepine 10, 11-epoxide, which was the main metabolite of carbamazepine in plasma, were assessed in sera from 30 adult patients with epilepsy on carbamazepine monotherapy. The binding characteristics of each compound were analyzed according to the two-site binding model. Association constants to the high-affinity binding site on alpha 1-acid glycoprotein (AAG) were 0.053 l/mumol for carbamazepine and 0.013 l/mumol for carbamazepine 10, 11-epoxide. The maximum binding capacities for drug-AAG binding were 49.2 mumol/l for carbamazepine and 48.1 mumol/l for carbamazepine-10, 11-epoxide. The products of the association constant and binding capacity for the lower-affinity site (i.e., the linear component of albumin binding site) were 1.273 for carbamazepine and 0.525 for carbamazepine 10, 11-epoxide. Within the total concentration range of each compound investigated, the contribution of drug-AAG binding to the total serum binding was relatively larger than that of drug-albumin binding.