Pharmacologic Profile of Naloxegol, a Peripherally Acting µ-Opioid Receptor Antagonist, for the Treatment of Opioid-Induced Constipation

Opioid-induced constipation (OIC) is a common side effect of opioid pharmacotherapy for the management of pain because opioid agonists bind to µ-opioid receptors in the enteric nervous system (ENS). Naloxegol, a polyethylene glycol derivative of naloxone and a peripherally acting µ-opioid receptor antagonist, targets the physiologic mechanisms that cause OIC. Pharmacologic measures of opioid activity and pharmacokinetic measures of central nervous system (CNS) penetration were employed to characterize the mechanism of action of naloxegol. At the human µ-opioid receptor in vitro, naloxegol was a potent inhibitor of binding (K i =7.42 nM) and a neutral competitive antagonist (p A 2 =7.95); agonist effects were