Abstracts

Rationale: Measurement of anti-epileptic drug (AED) concentration is a common practice to guide pharmacotherapy. A study had been previously conducted to examine carbamazepine concentration variability in elderly nursing home patients. However, there has not been a systematic evaluation of the variability of carbamazepine and lamotrigine in elderly community dwelling population, which generally has less co-morbidity than nursing home population. The purpose of this project was to determine the intra-individual variability of carbamazepine and lamotrigine concentrations following multiple measurements in elderly community dwelling patients.Methods: Data was obtained from the VA Cooperative Study 428, a randomized, double-blinded parallel group, monotherapy study of carbamazepine, gabapentin, and lamotrigine in 593 elderly patients with newly diagnosed seizures. For the variability assessment, only patients with at least three drug concentration measurements while on the same dose of the respective study drug for at least four weeks were included. Patients on potentially interfering concomitant medications were also excluded. A subtotal of 42 patients on carbamazepine and 72 patients on lamotrigine were used in the evaluations of concentration fluctuations.Results: The mean age (range) of patients on carbamazepine and lamotrigine was 69.9 (59 - 84) and 69.8 (59 - 92) respectively in the study. Mean total daily doses (ranges) were 561.9 (400 800) mg/day for carbamazepine and 143.8 (25 200) mg/day for lamotrigine. Carbamazepine concentrations varied by approximately 2.5-fold on average and fluctuations ranged from a minimum of 1.04-fold (12.24 to 12.67 mg/ml) to a maximum of 15.2-fold (0.85 to 12.89 mg/ml). Lamotrigine concentrations varied by approximately 1.8-fold on average and ranged from 1.06-fold (3 to 3.17 g/ml) to 8.6-fold (0.3 to 2.59 g/ml). There was no trend towards higher or lower carbamazepine or lamotrigine concentrations over time, and no observable differences in intra-individual variability over the age ranges in this study. Conclusions: In some elderly patients, carbamazepine and lamotrigine concentrations can vary substantially even while on stable dosing. The variability observed did not appear to be clearly related to any one factor available in the study, and the clinical consequence is unclear. As such, while the use of AED concentration measurements to guide therapy is useful and widely accepted, single measurements of carbamazepine and lamotrigine concentration should be used with caution for therapeutic drug monitoring, based on the currently limited understanding of the causes of fluctuations in these concentrations.