Carbamazepine-10,11-diol steady-state serum levels and renal excretion during carbamazepine therapy in adults and children

Abstract

Steady-state levels of carbamazepine (CBZ), CBZ-10,11-epoxide (CBZ-E), and 10,11-dihydro-10,11-trans-dihydroxy-CBZ (CBZ-diol) were monitored in 53 adults and 16 children, and 24-h urinary excretion of CBZ-E and CBZ-diol was measured in 25 adults and 8 children. The CBZ dose correlated significantly with the serum level of the metabolites but not with the CBZ level. The variability of the CBZ dose/level ratio was related to comedication. Similarly, comedication altered the serum CBZ-diol/CBZ ratio and, to a lesser extent, the CBZ-E/CBZ as well as the CBZ-diol/CBZ-E ratios. Fluctuations of the CBZ-diol levels during the day were less than half as high as CBZ fluctuations. Children had a higher CBZ dose/level ratio and a relatively lower serum CBZ-diol/CBZ ratio, possibly because they also had a higher renal clearance for CBZ-diol. The fraction of the CBZ dose excreted as urinary CBZ-diol was equal in adults and children (35.2 and 36.2%, respectively). The results of this study suggest that the steady-state serum CBZ-diol/CBZ ratio is a sensitive indicator of enzymatic induction and that it can be useful in determining if unexpected CBZ levels can be attributed to the rate of enzymatic conversion of CBZ.