Fingolimod (FTY720) in Severe Hepatic Impairment: Pharmacokinetics and Relationship to Markers of Liver Function

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.