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Type: Journal article
Title: Influence of cirrhosis on lamotrigine pharmacokinetics
Author: Marcellin, P.
De Bony, F.
Garret, C.
Altman, C.
Boige, V.
Castelnau, C.
Laurent-Puig, P.
Trinchet, J.
Rolan, P.
Chen, C.
Mamet, J.
Bidault, R.
Citation: British Journal of Clinical Pharmacology, 2001; 51(5):410-414
Publisher: Blackwell Publishing Ltd
Issue Date: 2001
ISSN: 0306-5251
Statement of
P. Marcellin, 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
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.
Keywords: Cirrhosis
DOI: 10.1046/j.1365-2125.2001.01389.x
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Pharmacology publications

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