纳地美定的作用原理是什么？

Principle of action

It was launched in Japan and the United States in 2017 and in the European Union in 2019 for the treatment of constipation caused by opioids.

Naldimedine is an opioid antagonist with binding affinity for k-opioid receptors. In tissues such as the gastrointestinal tract, naloxone acts as a peripherally acting μ-opioid receptor antagonist, thereby reducing the constipating effects of opioids. Naltrexone is a derivative of naltrexone to which a side chain has been added, increasing the molecular weight and polar surface area, thereby reducing its ability to cross the blood-brain barrier (BBB).

Naldimedine is also a substrate of the P-glycoprotein (P-gp) efflux transporter. Based on these properties, negligible CNS penetration of naltrmidine is expected at recommended dose levels, thus limiting the potential to interfere with centrally mediated opioid analgesia.

Naldimedine for opioid-induced constipation

Opioid-induced bowel dysfunction (OIBD) is a common complication in long-term opioid users and abusers. It is a burdensome disease that severely limits quality of life and is associated with increased health costs. OIBD affects up to 60% of patients with chronic non-cancer pain and more than 80% of patients with cancer pain and is one of the most common symptoms associated with opioid maintenance.

In a Phase III trial, naldemedine was more effective than placebo in increasing bowel movement frequency in patients taking opioids to treat constipation due to cancer pain or chronic non-cancer pain. Naldemedine has also been associated with improvements in constipation-related symptoms and quality of life. Naldemedine is generally well tolerated, including over the long term. Because naldemedine specifically targets opioid receptors in the gastrointestinal (GI) tract and does not cross the blood-brain barrier, it does not cause opioid withdrawal symptoms or interfere with centrally mediated opioid analgesia. Consistent with its mechanism of action, the most common adverse reactions are gastrointestinal in nature.

In summary, the current data suggest that naldemedine is an effective and generally well-tolerated treatment option for patients with opioid-induced constipation with cancer pain or chronic non-cancer pain, and is available in a convenient once-daily oral dose.

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