Autoinduction of carbamazepine metabolism in children examined by a stable isotope technique

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Abstract
Autoinduction of carbamazepine (CBZ) metabolism was investigated in 3 [epileptic] children (10 to 13 yr old) using tetradeuterium-labeled CBZ (CBZ-D4). CBZ and CBZ-D4 given as a mixture prior to treatment had almost identical kinetics in each patient. During maintenance therapy with CBZ, part of the CBZ was exchanged for CBZ-D4 on 3 occasions. The clearance of CBZ-D4 given on the 2nd day of therapy was 0.036 .+-. 0.003 1 .cntdot. kg-1 .cntdot. h-1, whereas it had been 0.028 .+-. 0.003 before treatment. After 17 to 32 days of treatment, clearance doubled (0.056 .+-. 0.010) but during the next 4 mo., there was no further increase, indicating that the autoinduction was complete within 1 mo. As a corollary, there was a decrease in steady-state plasma levels.