Advantage of Extracellular Water Volume for the Relation between Serum Carbamazepine Concentration and Transformed Daily Dose

Abstract

We conducted a study to clarify the most suitable factors related to the carbamazepine daily dose (D) with the serum concentration (Ct).Therapeutic drug monitoring data obtained from epileptic patients who were chronically treated with single and repetitive oral administrations of carbamazepine (CBZ). The 119 steadystate data were used.First, when the extracellular water volume (VECW) was employed as a transforming factor, Ct/(D/VECW) ratio was found to be independent of the patient's age. In addition, a multiple regression analysis revealed that Ct was dependent on only D/VECW. From these findings, we concluded that Ct could only be related with D/VECW.Next, a l -compartment model including two assumptions that CBZ binds to plasma protein and the distribution volume of free-CBZ is proportional to VECW, was postulated for our analysis. At steady-state, Ct was expressed as follows:C1=αX (1+KaCbs+αKaX)/(1+αKaX) (X=D/VECW.α, Ka, Cbs: parameter)The parameter values were estimated by the nonlinear least squares method as α, Ka and Cbs were 0.013, 1.6 and 12.8, respectively.The plasma protein binding ratios were 92.3, 90.2 and 87.1 (%) when the serum CBZ concentrations were 6, 8 and 10 [μg/mL], respectively. These values closely corrected with those reported previously.As a result, VECW is considered to be a suitable transforming factor for the relation between Ct and D, and our model seems to be approriate.