Fluctuations in salivary carbamazepine and carbamazepine-10,11-epoxide concentrations during the day in epileptic children.

Abstract

Hourly salivary concentrations of carbamazepine (CBZ) and carbamazepine-10,11-epoxide (EP) were studied during 2 consecutive days in a group of epileptic children receiving twice daily CBZ monotherapy either as the tablet or syrup formulation. Relatively large fluctuations were observed for both CBZ (mean, 57%; range, 32-100%) and EP (mean, 97%; range, 19-189%) during a dosage interval. However, concentrations of EP were generally much lower, approximately 34% of corresponding CBZ levels, and in absolute terms the concentration-time curves for EP appeared much less variable. Further evidence supporting extensive CBZ concentration fluctuations during the day was provided by an additional group of 30 epileptic children receiving CBZ monotherapy whose time of dosage was manipulated to achieve peak and trough concentrations during assessment with a psychomotor test battery. Changes in salivary CBZ concentrations within subjects ranged from 4 to 272% (median, 65%), excluding two atypical cases who showed greater than 10-fold increases in the expected high concentration. These results suggest that in children there is a substantial risk of error in the interpretation of CBZ concentrations from a single sample without consideration of the time of last dose. The implications of these findings for clinical treatment with regard to the appearance of side effects and changes in psychomotor function are discussed.