High Predictability of Plasma Lacosamide and No Relevant Differences by Age and Gender Following Normalization (P4.261)

OBJECTIVE: To assess the effect of age and gender on the pharmacokinetic (PK) parameters of oral lacosamide. BACKGROUND: Lacosamide is a newer antiepileptic drug, indicated for the treatment of partial-onset seizures (POS) in adults. Evaluating differences in the lacosamide PK profile due to age or gender differences could provide additional considerations for therapeutic regimens. DESIGN/METHODS: Data were extracted from two Phase I studies; the first included female subjects aged 18-40 years (lacosamide 400mg/day) whereas the second included male and female subjects 蠅65 years (200mg/day), and male subjects 18-45 years (200mg/day). Area under the concentration time curve over a dosing interval at steady state (AUCtau,ss) and maximum measured concentration in a dosing interval at steady state (Cmax,ss) were determined by non-compartmental methods. Statistical comparisons were performed after log-transformation based on analysis of variance. Results were compared to a population PK study of lacosamide in patients with POS. RESULTS: Sixty-six subjects were stratified by age group and gender. AUCtau,ss and Cmax,ss tended to show higher values in females compared to males, and also in elderly vs. young subjects. Differences between groups were smaller when normalized by body weight, height, fat free mass (FFM), lean body weight (LBW), and by volume of distribution (Vd). 90[percnt] confidence intervals for the ratio of AUCtau,ss and Cmax,ss, over age and gender comparisons fell within the range of 80-125[percnt] when normalized by Vd. The same was true for Cmax,ss normalized by LBW or FFM. Population PK study data confirmed these results in patients with POS. CONCLUSIONS: Age- and gender-related differences in lacosamide PK parameters for both healthy subjects and patients with POS are mostly due to inter-individual variability of Vd, explained to a large extent by differences in body composition. Results were confirmed by data from a population PK study. Study Supported by: UCB Pharma. Disclosure: Dr. Schaefer has received personal compensation for activities with UCB Pharma as an employee. Dr. Cawello has received personal compensation for activities with UCB Pharma as an employee. Dr. Andreas has received personal compensation for activities with UCB Pharma as an employee.