title: Pharmacokinetics of fingolimod and metabolites in subjects with severe renal impairment: An open-label, single-dose, parallel-group study.
abstract: OBJECTIVE
  This study assessed the pharmacokinetics and tolerability of fingolimod and its metabolites in severe renal impairment and healthy subjects.
  
  
  METHODS
  In this single-dose, open-label study, 9 severe renal impairment subjects and 9 demographically matched healthy subjects were included. Each subject received a single oral dose of fingolimod 1.25 mg, and their blood and urine samples were assessed. The pharmacokinetics of fingolimod and its metabolites, fingolimod-phosphate (active metabolite, fingolimod-P), M2, and M3, were compared in both groups. Safety and tolerability were also assessed.
  
  
  RESULTS
  In severe renal impairment subjects, mean±standard deviation values of Cmax (ng/mL) of fingolimod and fingolimod-P were 0.878±0.256 and 1.13±0.293 vs. 0.653±0.138 and 0.904±0.229 in healthy subjects, respectively. The overall drug exposures (AUCinf (ngxh/mL)) for fingolimod and fingolimod-P were 131±90.7 and 75.5±33.6 in severe renal impairment subjects vs. 82.3±36.9 and 65.9±30.6 in healthy subjects, respectively. t1/2 (hours) for fingolimod and fingolimod-P was comparable in severe renal impairment subjects (94±53 and 95±50) and healthy subjects (85±25 and 101±46). All adverse events were as expected for fingolimod 1.25 mg.
  
  
  CONCLUSIONS
  The exposure to fingolimod and fingolimod-P was moderately increased (90% CI, 0.94-2.18) in severe renal impairment subjects, while half-lives and protein binding were similar to those in healthy subjects. Given that these changes are not clinically meaningful, fingolimod dose adjustment is considered unnecessary in patients with mild, moderate, or severe renal impairment.
authors: Olivier J
authors: OJ
authors: David
authors: Maxwell
authors: M
authors: Pryce
authors: Karin
authors: K
authors: Meiser
authors: Franck
authors: F
authors: Picard
authors: Corinne
authors: C
authors: Emotte
authors: Zhanna
authors: Z
authors: Kobalava
authors: Valentin
authors: V
authors: Moiseev
authors: Robert
authors: R
authors: Schmouder
mesh_terms: D000328:Adult; D005260:Female; D000068876:Fingolimod Hydrochloride / Q000009:adverse effects / Q000493:pharmacokinetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D051437:Renal Insufficiency / Q000378:metabolism*
chemical_list: D000068876:Fingolimod Hydrochloride