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Clinical Trial
. 2001 May;51(5):410-4.
doi: 10.1046/j.1365-2125.2001.01389.x.

Influence of cirrhosis on lamotrigine pharmacokinetics

P Marcellin  1 , F de Bony, C Garret, C Altman, V Boige, C Castelnau, P Laurent-Puig, J C Trinchet, P Rolan, C Chen, J P Mamet, R Bidault
Affiliations
Clinical Trial

Influence of cirrhosis on lamotrigine pharmacokinetics

P Marcellin et al. Br J Clin Pharmacol. 2001 May.

Abstract

Aims: 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.

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

Results: 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%).

Conclusions: 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.

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Figures

Figure 1
Figure 1
Median lamotrigine plasma concentration vs time profiles following a single 100 mg oral dose in healthy volunteers (•), patients with moderate cirrhosis (○), patients with severe cirrhosis without ascites (▾) and patients with severe cirrhosis with ascites (▿).
Figure 2
Figure 2
The relationship between lamotrigine oral clearance (CL/F) and Child-Pugh score
See this image and copyright information in PMC

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