Impact of Renal Impairment on the Pharmacokinetics of Apremilast and Metabolite M12

The pharmacokinetics of apremilast and its major metabolite M12 were evaluated in subjects with varying degrees of renal impairment. Men and women with renal impairment (estimated glomerular filtration rate, 60-89 mL/min [mild, n = 8], 30-59 mL/min [moderate, n = 8], or <30 mL/min [severe, n = 8]) or demographically healthy matched (control) subjects (n = 24) received a single oral dose of apremilast 30 mg. Plasma apremilast and metabolite M12 concentrations were determined, and pharmacokinetic parameters were calculated from samples obtained predose and up to 72 hours postdose. In subjects with mild to moderate renal impairment, apremilast pharmacokinetic profiles were similar to healthy matched subjects. In subjects with severe renal impairment, apremilast elimination was significantly slower, and exposures based on area under the plasma concentration-versus-time curve from time zero extrapolated to infinity and maximum observed plasma concentration were increased versus healthy matched subjects. Metabolite M12 pharmacokinetic profiles for subjects with mild renal impairment were similar to those of the healthy matched subjects; however, they were increased in both the moderate and severe renally impaired subjects. Dose reduction of apremilast is recommended in individuals with severe renal impairment, but not in those with mild to moderate renal impairment.