Pharmacokinetics, Safety, and Tolerability of Lamotrigine Chewable/Dispersible Tablet Following Repeat‐Dose Administration in Healthy Chinese Volunteers

Abstract

In this open-label, single-center study, the pharmacokinetics, safety, and tolerability of lamotrigine chewable/dispersible tablets were assessed in healthy Chinese volunteers. Each volunteer (N=16) received repeat doses of oral lamotrigine titrated from 25mg to 50mg to 100mg over 42days and was followed up for 10-17days. Safety and tolerability were assessed throughout the study. Lamotrigine pharmacokinetic parameters were estimated using noncompartmental analysis. Overall, 15 (94%) volunteers completed the study. Lamotrigine serum concentrations peaked 2.5hours postdose, with a mean terminal half-life of 36.8hours. The apparent lamotrigine oral clearance was 1577.88mL/h. The accumulation ratios (day14 vs day1) were 2.53 and 2.58 for area under the curve and peak concentration, respectively. Lamotrigine 25to 100mg once daily exhibited dose-proportional pharmacokinetics (based on area under the curve and peak concentration), following repeat dosing. Nine volunteers reported adverse events, 2 experienced oropharyngeal pain, each receiving 25mg and 50mg. One volunteer withdrew due to an increase in liver enzymes. No deaths, serious adverse effects, or skin rashes were reported during the study. No new safety concerns were observed. Overall, the pharmacokinetic profiles after repeat doses of lamotrigine chewable/dispersible tablets once daily in a Chinese population were similar to those observed in Western populations.