Factors Influencing Simultaneous Concentrations of Total and Free Carbamazepine and Carbamazepine-10, 11-Epoxide in Serum of Children with Epilepsy

Abstract

Various factors that may influence the simultaneous concentration of total and free carbamazepine (CBZ) and carbamazepine-10,11-epoxide (CBZ-E)in serum of 68 children (mean age 11.8 .+-. 4.5 years) with epilepsy were assessed. Separation of free and bound drug fractions was achieved by ultrafiltration, and CBZ and CBZ-E concentrations were determined using a sensitive high pressure liquid chromatographic technique. Thirty children were on CBZ monotherapy. Both total CBZ and CBZ-E serum concentrations correlated significantly with their respective free serum concentrations. CBZ was 81 .+-. 3% and CBZ-E 63 .+-. 9% bound. There was no correlation between the CBZ dose and either CBZ total or free serum concentrations. A statistically significant correlation was, however, observed between CBZ dose and simultaneous CBZ-E total and free concentrations. CBZ total and free concentrations correlated significantly with those of total CBZ-E. A significant negative correlations was observed between age and total (r = -0.49, p < 0.01) and free (r = -0.43, p < 0.025) CBZ-E/CBZ ratios. Concomitant drug therapy (phenytoin, phenobarbitone, and sodium valproate) significantly elevated CBZ-E CBZ ratios.