Alvimopan dihydrate

Alvimopan dihydrate (CAS No. 170098-38-1) is a selective μ-opioid receptor antagonist with a half-maximal inhibitory concentration (IC₅₀) of 1.7 nM for the μ-opioid receptor. Opioid receptors belong to the G protein-coupled receptor family, with opioid substances as their specific ligands.

The core pharmacokinetic characteristic of this drug lies in its long-acting effect: its dissociation half-life from the μ-opioid receptor (T₁/₂ = 30-44 minutes) is significantly longer than that of other similar antagonists such as N-methylnaltrexone (T₁/₂ = 0.46 minutes) and naloxone (T₁/₂ = 0.82 minutes), and is comparable to that of the long-acting partial agonist buprenorphine (T₁/₂ = 44 minutes). Furthermore, pre-incubation with the μ-opioid receptor notably enhances its affinity and potency, which further confirms its long-acting property [1].

In clinical applications, for patients with opioid-induced bowel dysfunction (OBD), a 6-week oral treatment regimen with alvimopan (0.5 mg twice daily, 1 mg once daily, or 1 mg twice daily) has shown significant efficacy: within the last three weeks of treatment, the average weekly spontaneous bowel movement (SBM) frequency of patients increased by 1.71 times (0.5 mg twice daily), 1.64 times (1 mg once daily), and 2.25 times (1 mg twice daily), respectively. In terms of safety, its adverse reactions are mainly abdominal pain, nausea, and diarrhea, with an incidence rate similar to that of the placebo group. Importantly, it does not affect the analgesic efficacy of opioid drugs, and can restore gastrointestinal function and relieve OBD symptoms while maintaining the analgesic effect [2].

References:

[1].  Cassel JA, Daubert JD, DeHaven RN. [(3)H]Alvimopan binding to the micro opioid receptor: comparative binding kinetics of opioid antagonists. Eur J Pharmacol, 2005, 520(1-3): 29-36.

[2].  Webster L, Jansen JP, Peppin J, et al. Alvimopan, a peripherally acting mu-opioid receptor (PAM-OR) antagonist for the treatment of opioid-induced bowel dysfunction: results from a randomized, double-blind, placebo-controlled, dose-finding study in subjects taking opioids for chronic non-cancer pain. Pain, 2008, 137(2): 428-440.