The pathophysiology of CKD-aP is thought to be multifactorial, including:
an imbalance in the endogenous opioid system (e.g., overexpression of mu-opioid receptors [MORs] and concomitant downregulation of KORs)
systemic inflammation
KORSUVA’s mechanism of action*
KORSUVA targets KORs, with low central nervous system (CNS) penetration and with no binding or functional activity at mu-opioid receptors.
KORSUVA has a hydrophilic structure, which minimizes its passive diffusion (permeability) and active transport across the blood-brain barrier, thus limiting penetration into the CNS.
The activation of KORs on peripheral sensory neurons and immune cells by KORSUVA are considered mechanistically responsible for the antipruritic and anti-inflammatory effects.
Pharmacodynamics
In clinical studies, there were no signals of abuse, misuse, diversion, dependence, or withdrawal with KORSUVA.1
* Comparative clinical significance has not been established.