Korsuva

Difelikefalin is a selective kappa opioid receptor agonist with low central nervous system penetration.
The physicochemical properties of difelikefalin (hydrophilic, synthetic D-amino acid peptide with high polar surface area and charge at physiological potential of hydrogen (pH)) minimise its passive diffusion (permeability) and active transport across membranes, thus limiting penetration into the central nervous system.
The pathophysiology of chronic kidney disease associated pruritus is thought to be multifactorial, including systemic inflammation and an imbalance in the endogenous opioid system (for example, overexpression of mu opioid receptors and concomitant downregulation of kappa opioid receptors).
Opioid receptors are known to modulate itch signals and inflammation, with kappa opioid receptor activation reducing itch and producing immunomodulatory effects.
The activation of kappa opioid receptors on peripheral sensory neurons and immune cells by difelikefalin are considered mechanistically responsible for the antipruritic and anti-inflammatory effects.
Abuse and dependence potential has been examined in rat studies, which do not indicate likely potential for physical dependence or abuse in rats.