This study reports key differences in the pharmacokinetics of difelikefalin in subjects on HD relative to healthy subjects, including higher total exposure and longer plasma half-life.

In healthy subjects, difelikefalin was excreted primarily into urine with metabolites accounting for < 1% of the total dose. In subjects on HD, elimination was primarily through feces and dialysate with a series of low-abundance metabolites identified in feces, ranging from 0.2 to 2.4% of the total dose.

In both healthy subjects and subjects on HD, difelikefalin was the predominant component in plasma, representing > 99% of circulating radioactivity.