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Fingolimod (FTY720) in Severe Hepatic Impairment: Pharmacokinetics and Relationship to Markers of Liver Function
Author(s) -
Kovarik John M.,
Schmouder Robert L.,
Hartmann Stefan,
Riviere GillesJacques,
Picard Franck,
Voss Brigitta,
Weiss Markus,
Wagner Frank,
Schmidt Hartmut H.J.
Publication year - 2006
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1177/0091270005283464
Subject(s) - fingolimod , medicine , pharmacokinetics , prothrombin time , liver function , albumin , bilirubin , liver function tests , area under the curve , gastroenterology , endocrinology , pharmacology , multiple sclerosis , immunology
The authors assessed the impact of severe hepatic impairment on the disposition of fingolimod—a sphingosine‐1‐phosphate receptor immunomodulator primarily metabolized by CYP4F2—in 6 patients and 6 matched healthy controls who received a single 5‐mg oral dose. Compared with healthy controls, severe hepatic‐impaired subjects had a doubled area under the concentration time curve (AUC) and 50% prolonged elimination half‐life but a similar peak blood concentration. When these data were combined with those from a previous study in mild and moderate hepatic‐impaired subjects, there were significant positive correlations between fingolimod AUC versus bilirubin (r = 0.683) and prothrombin time (r = 0.777) and a significant negative correlation versus albumin (r = 0.578), confirming the importance of liver function for fingolimod clearance. For patients with severe hepatic impairment (Child‐Pugh class C), a standard first dose of fingolimod could be given followed by a maintenance dose that is reduced by half from the normal maintenance dose.