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 (ng×h/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. © 2015 Dustri-Verlag Dr. K. Feistle.