The following is a summary of “Impact of renal impairment on the pharmacokinetic profile of intravenous difelikefalin, a kappa opioid receptor agonist for the treatment of pruritus,” published in the October 2024 issue of Nephrology by Spencer et al. 

Researchers conducted a retrospective study to assess the pharmacokinetics (PK) of intravenous difelikefalin, approved for treating pruritus in adults with chronic kidney disease (CKD) on hemodialysis (HD). The study included healthy subjects, patients who are non–dialysis-dependent (NDD), and those with end-stage renal disease (ESRD) on hemodialysis. 

They assessed the PK and safety of a single IV dose of difelikefalin (3.0 mcg/kg) in NDD patients with renal impairment vs healthy controls. Then, they compared 3 doses (0.5, 1.0, or 2.5 mcg/kg) with placebo in patients with HD, given after dialysis over a 1-week period. 

The results showed that patients who are NDD (N = 36) and those with mild renal impairment had similar exposure to healthy subjects, while patients with moderate or severe impairment exhibited higher total exposure. Patients with severe impairment had higher exposure than those with moderate impairment (i.e., exposure in severe NDD > moderate NDD > mild NDD ≈ healthy subjects). Clearance decreased as renal impairment increased. In patients with ESRD undergoing HD (N = 19), difelikefalin demonstrated dose proportionality, was mostly cleared by dialysis, and reached a steady state by the second dose on day 3. Safety findings were consistent with the known profile of IV difelikefalin. 

The study concluded that IV difelikefalin was well tolerated, with similar exposure in patients with mild renal impairment and healthy subjects. They found reduced clearance and higher exposure in moderate to severe renal impairment, with dose proportionality and effective dialysis clearance in patients with end-stage renal disease. 

Source: bmcnephrol.biomedcentral.com/articles/10.1186/s12882-024-03790-w