Find, compare & contact
Naldemedine API Manufacturers & Suppliers

General Description:

Naldemedine, identified by CAS number 916072-89-4, is a notable compound with significant therapeutic applications. Naldemedine is an opioid receptor antagonist . It is a modified form of to which a side chain has been added to increase molecular weight and polar surface area resulting in restricted transport across the blood brain barrier. Naldemedine was approved in 2017 in both the US and Japan for the treatment of Opioid-induced Constipation.

Indications:

This drug is primarily indicated for: For the treatment of opioid-induced constipation . Its use in specific medical scenarios underscores its importance in the therapeutic landscape.

Metabolism:

Naldemedine undergoes metabolic processing primarily in: Naldemedine is mainly metabolized to nor-naldemedine by CYP3A . Some metabolism to naldemedine-3-glucuronide occurs via UGT1A3. Both metabolites are acitive but less potent than naldemedine. The relative exposures of these metabolites are 9-13% and <3% for nor-naldemedine and naldemedine-3-glucuronide respectively. Naldemedine is also cleaved in the intestine to form benzamidine and naldemedine carboxylic acid. This metabolic pathway ensures efficient processing of the drug, helping to minimize potential toxicity and side effects.

Absorption:

The absorption characteristics of Naldemedine are crucial for its therapeutic efficacy: Tmax is 0.75 h . Administration with a high-fat meal reduces Cmax by 35% and increases Tmax to 2.5 h. The drug's ability to rapidly penetrate into cells ensures quick onset of action.

Half-life:

The half-life of Naldemedine is an important consideration for its dosing schedule: The terminal elimination half life is 11 h . This determines the duration of action and helps in formulating effective dosing regimens.

Protein Binding:

Naldemedine exhibits a strong affinity for binding with plasma proteins: Naldemedine is 93-94% bound to human plasma proteins . This property plays a key role in the drug's pharmacokinetics and distribution within the body.

Route of Elimination:

The elimination of Naldemedine from the body primarily occurs through: 57% of naldemedine is excreted in the urine with 16-18% as the parent compound and 35% is excreted in the feces . Understanding this pathway is essential for assessing potential drug accumulation and toxicity risks.

Volume of Distribution:

Naldemedine is distributed throughout the body with a volume of distribution of: The apparent volume of disribution during the terminal phase is 155 L. This metric indicates how extensively the drug permeates into body tissues.

Pharmacodynamics:

Naldemedine exerts its therapeutic effects through: Naldemedine is an opioid receptor antagonist with restricted movement across the blood brain barrier . This allows it to antagonize the periperal effects of opioid drugs such as constipation without interfering with the effects on the central nervous system. The drug's ability to modulate various physiological processes underscores its efficacy in treating specific conditions.

Mechanism of Action:

Naldemedine functions by: Naldemedine binds to and antagonizes mu-, delta-, and kappa-opioid receptors . The binding of opioid agonists to peripheral mu-opioid receptors slows the transit of feces through the intestine resulting in constipation. By antagonizing mu-opioid receptors, naldemedine inhibits this effect. This mechanism highlights the drug's role in inhibiting or promoting specific biological pathways, contributing to its therapeutic effects.

Toxicity:

Classification:

Naldemedine belongs to the class of organic compounds known as morphinans. These are polycyclic compounds with a four-ring skeleton with three condensed six-member rings forming a partially hydrogenated phenanthrene moiety, one of which is aromatic while the two others are alicyclic, classified under the direct parent group Morphinans. This compound is a part of the Organic compounds, falling under the Alkaloids and derivatives superclass, and categorized within the Morphinans class, specifically within the None subclass.

Categories:

Naldemedine is categorized under the following therapeutic classes: Alimentary Tract and Metabolism, Alkaloids, Drugs for Constipation, Drugs that are Mainly Renally Excreted, Heterocyclic Compounds, Fused-Ring, Morphinans, Opiate Alkaloids, Opioid Antagonists, Peripheral Opioid Receptor Antagonists, Phenanthrenes, UGT1A3 substrates. These classifications highlight the drug's diverse therapeutic applications and its importance in treating various conditions.

Experimental Properties:

Further physical and chemical characteristics of Naldemedine include:

• Water Solubility: Slightly soluble