A Comprehensive Study of the Relation Between Serum Concentrations, Concentration Ratios, and Level/Dose Ratios of Carbamazepine and Its Metabolites with Age, Weight, Dose, and Clearances in Epileptic Children

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Abstract
Summary: We made a comprehensive study of the relation between age, weight, carbamazepine (CBZ) dose, total clearance (TC), and intrinsic clearance (IC) and concentrations, concentration ratios, and level/dose ratios of CBZ, carbamazepine‐10,11‐epoxide (CBZ‐E) and trans‐10,11‐dihydroxy‐10,11‐dihydro‐carbamazepine (CBZ‐H) in a group of epileptic children receiving CBZ monotherapy. Body weight and age showed negative correlations with TC, IC, CBZ dose, and CBZ‐E/CBZ and CBZ‐HI CBZ concentration ratios, and had positive relation with CBZ, CBZ‐E, and CBZ‐H level/dose ratios. These results indicate decreased CBZ metabolism with patient maturity. Correlations between CBZ dose with TC, IC, and the concentration ratios of CBZ‐E/CBZ, CBZ‐H/CBZ‐E, and CBZ‐H/CBZ were positive. CBZ dose also had negative associations with CBZ and CBZ‐E level/dose ratios, indicating dose‐dependent autoinduction of CBZ metabolism. Our data suggest that weight, age, and CBZ dose have less influence on epoxidehydrolase activities than on epoxidase activities. The CBZ‐E/CBZ concentration ratio can be used as an indicator of the degree of autoinduction of CBZ metdbohn, even in patients receiving CBZ monotherapy.