How suitable are currently used carbamazepine immunoassays for quantifying carbamazepine-10,11-epoxide in serum samples?

Abstract

The pharmacologic activity of the metabolite carbamazepine-10,11-epoxide (CBZ-E) is similar to that of carbamazepine (CBZ). As a result, determining the CBZ + CBZ-E concentration would offer a better correlation with therapeutic or toxic effects than measurement of the parent drug alone. However, the most upto-date CBZ immunoassays are not able to quantitatively measure CBZ-E. Trough serum concentrations of CBZ were measured in 116 patients either in monotherapy (n = 66) or in polytherapy with other antiepileptic drugs (n = 50) using the Dade Dimension and Roche Cobas Integra immunoassays. The results were compared with those obtained for CBZ + CBZ-E by high-performance liquid chromatography (HPLC). The Dade Dimension immunoassay gave a concentration-dependent CBZ-E cross-reactivity for the metabolite levels present in the samples studied (mean, 1.41 mg/L; range, 0.0-7.6 mg/L), whereas the Roche Cobas Integra gave a negligible cross-reactivity. The results provided by the Dade Dimension immunoassay only presented a clinically significant difference with regard to the CBZ + CBZ-E value in the group of patients comedicated with valproic acid. The results of this immunoassay revealed a high correlation and small standard error of the estimate for the total group of patients with the composite results of parent drug + metabolite obtained by HPLC (r = 0.993, ma68 = 0.22 mg/L), with a regression line CBZ + CBZ-E = 1.09 CBZ(Dade Dimension) + 0.07. By using the Dade Dimension immunoassay, it is possible to make a clinically valid estimate of the CBZ + CBZ-E concentrations in patients treated with CBZ in monotherapy and polytherapy. However, other immunoassays with a lower CBZ-E cross-reactivity are not suitable for this estimate to be made at increased metabolite levels.