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 correlation was observed between age and total (r = -0.49, p less than 0.01) and free (r = -0.43, p less than 0.025) CBZ-E/CBZ ratios. Concomitant drug therapy (phenytoin, phenobarbitone, and sodium valproate) significantly elevated CBZ-E/CBZ ratios.