Influence of cirrhosis on lamotrigine pharmacokinetics

Lamotrigine, an antiepileptic drug, is cleared from the systemic circulation mainly by glucuronidation. The possibility of changes in the pharmacokinetics of lamotrigine in plasma owing to hepatic dysfunction has been evaluated.

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 nine with severe cirrhosis, who had a 29 day blood sampling period.

The pharmacokinetics of lamotrigine were comparable between the patients with moderate cirrhosis (corresponding to Child-Pugh grade A) and the healthy subjects. Plasma oral clearance mean ratios (90% confidence interval) in patients with severe cirrhosis without or with ascites (corresponding, respectively, to Child-Pugh grade B and C) to healthy subjects were, respectively, 60% (44%, 83%) and 36% (25%, 52%). Plasma half-life mean ratios (90% confidence interval) in these two patient groups to healthy subjects were, respectively, 204% (149%, 278%) and 287% (202%, 408%).

Lamotrigine administered as a single oral dose of 100 mg was well tolerated in all groups. Initial, escalation and maintenance doses should generally be reduced by approximately 50 or 75% in patients with Child-Pugh Grade B or C cirrhosis. Escalation and maintenance doses should be adjusted according to clinical response.