The role of naldemedine in the treatment of opioid-induced constipation

The use of opioid receptor agonists and antagonists in the treatment of patients with advanced chronic kidney disease and undergoing renal replacement therapy

“…The latter group includes N-methylnaltrexone, naloxegol, alvimopan and naldemedine [25]. PAMORAs are modified derivatives of naloxone or naltrexone, whose molecules have lost their ability to penetrate the BBB, blocking opioid receptors in the gastrointestinal tract without impairing analgesia [26,27].…”

“…Alvimopan is a μ-receptor antagonist that is approved in the United States for the short-term treatment of patients with postoperative intestinal obstruction [26,27].…”

“…Naldemedine is a naltrexone derivative, an antagonist of μ-, κ-, δ-opioid receptors [22,23,27,37]. Its penetration into the CNS is negligible [26,27]. This drug, which is metabolised mainly by CYP3A4 to nor-naldemedine, undergoes significantly less coupling to glucuronic acid [26].…”

“…Its penetration into the CNS is negligible [26,27]. This drug, which is metabolised mainly by CYP3A4 to nor-naldemedine, undergoes significantly less coupling to glucuronic acid [26]. Naldemedine is rapidly absorbed from the gastrointestinal tract, 57% is excreted in the urine and 35% in the faeces [25].…”

“…The excretion of naldemedine in patients with renal impairment, including ESRD patients who need haemodialysis, is not affected and the pharmacokinetics is similar to that in individuals with normal renal function, in whom 16-18% is excreted unchanged in the urine. Naldemedine is eliminated to a small extent (2.7%) during haemodialysis [26]. Plasma concentrations of this drug in ESRD patients who need dialysis are similar following naldemedine administration before or after haemodialysis, indicating that naldemedine is not removed during haemodialysis [37].…”