Effect of Age and Sex on Lacosamide Pharmacokinetics in Healthy Adult Subjects and Adults with Focal Epilepsy

Background and Objective Age- and sex-related differences in body composition could affect the pharmacokinetic parameters of administered drugs. The purpose of this post hoc analysis was to investigate the influences of age and sex on the pharmacokinetics of lacosamide. Methods This post hoc analysis used pharmacokinetic data taken at steady state from (i) two phase I studies of oral lacosamide in healthy adult subjects ( n = 66), and (ii) a population pharmacokinetic analysis carried out using data from two phase III studies of adjunctive oral lacosamide in adults ( n = 565) with focal epilepsy taking 1–3 concomitant anti-epileptic drugs. Phase I data were stratified by age and sex as ‘younger female’ (aged 18–40 years), ‘younger male’ (aged 18–45 years) or ‘elderly male/female’ (aged ≥65 years), then normalized by body weight (lean body weight or fat-free mass), height or volume of distribution, and analysed using non-compartmental analysis. Population pharmacokinetic data were stratified by sex and analysed using a one-compartment model. Results Minor numerical differences between lacosamide exposure [the area under the concentration–time curve at steady state over the dosage interval (AUC τ,ss )] and the maximum plasma concentration at steady state ( C max,ss ) in subjects of different ages or sexes were noted. The differences could be explained by a scaling factor between the drug applied and the plasma concentration. Following normalization by lean body weight or volume of distribution, an analysis of relative bioavailability resulted in 90 % confidence intervals of the ratios for AUC τ,ss and C max,ss for age (elderly to younger) or sex (male to female) falling within the range accepted for equivalence (80–125 %); without normalization, the 90 % confidence intervals were outside this range. Minor numerical differences in lacosamide plasma concentrations were noted in the comparison between male and female patients (aged 16–71 years) with focal epilepsy. Simulations using different body weights demonstrated a minimal effect of body weight on lacosamide plasma concentrations in adult patients with focal epilepsy. Conclusion Age and sex had no relevant effects on the rates of absorption and elimination of lacosamide in this post hoc analysis, as the minor numerical differences could be explained by the main scaling factor for body weight or volume of distribution. The pharmacokinetic profile of lacosamide was unaffected by age or sex in adults with f