Use of stable labelled carbamazepine to study its kinetics during chronic carbamazepine treatment

The kinetics of carbamazepine using stable labelled 15N-carbamazepine was studied in 4 epileptic patients who had been treated with it for at least 6 months. There was a decrease in half-life (12.3 +/- 0.8 h) and an increase in total plasma clearance (58.0 +/- 6.5 ml/min) as compared to single dose studies, which provide further evidence that carbamazepine induces its own metabolism during long-term treatment. Analysis of the urinary metabolites indicated induction of the epoxide-trans-diol pathway. Predicted and observed steady-state plasma levels were in good agreement, thus demonstrating that the use of stable labelled drugs is a useful technique to elucidate changes in kinetics and metabolism which may occur in patients during long-term treatment.