Influence of cirrhosis on lamotrigine pharmacokinetics

Aims Lamotrigine, an antiepileptic drug, is cleared from the systemic circu lation mainly by glucuronidation. The possibility of changes in the pharmac okinetics of lamotrigine in plasma owing to hepatic dysfunction has been ev aluated. Methods Thirty-six subjects, including 24 patients with various degrees of liver cirrhosis and 12 healthy volunteers received a single 100 mg dose of lamotrgine. Blood samples were taken for 7 days in all subjects, except nin e with severe cirrhosis, who had a 29 day blood sampling period. Results The pharmacokinetics of lamotrigine were comparable between the pat ients with moderate cirrhosis (corresponding to Child-Pugh grade A) and the healthy subjects. Plasma oral clearance mean ratios (90% confidence interv al) in patients with severe cirrhosis without or with ascites (correspondin g, respectively, to Child-Pugh grade B and C) to healthy subjects were, res pectively, 60% (44%, 83%) and 36% (25%, 52%). Plasma half-life mean ratios (90% confidence interval) in these two patient groups to healthy subjects w ere, respectively, 204% (149%, 278%) and 287% (202%, 408%). Conclusions Lamotrigne administered as a single oral dose of 100 mg was wel l tolerated in all groups. Initial, escalation and maintenance doses should generally be reduced by approximately 50 or 75% in patients with Child-Pug h Grade B or C cirrhosis. Escalation and maintenance doses should be adjust ed according to clinical response.