Grapiprant API Manufacturers

General Description:

Grapiprant, identified by CAS number 415903-37-6, is a notable compound with significant therapeutic applications. Grapiprant, also known as AT-001 and CJ-023, is a drug from the piprant class. These molecules were derived from acylsulfonamide and are characterized to be a novel series of para-N-acylaminomethylbenzoic acid known to be prostaglandin receptor antagonists. This type of molecules is currently in development for veterinary patients. This class of drugs was defined in 2013 by the World Health Organization. Grapiprant has been approved in March 2016 by the FDA's Center for Veterinary Medicine as a non-cyclooxygenase inhibiting NSAID for veterinary use.

Indications:

This drug is primarily indicated for: The effects of grapiprant have been investigated in the area of analgesia and anti-inflammation due to the effects that have been reported about this molecule. This molecule has been approved and widely accepted to be used in veterinary for pain reduction in arthritis. In humans, it has been researched to be used in the control of pain and inflammation associated with osteoarthritis. The effect of grapiprant can be explained through the function of prostaglandin E2 (PGE2) which is a key mediator of swelling redness and pain which are classic signs of inflammation. The effect of PGE2 results from its action through four receptor EP1, EP2, EP3 and EP4 from which the EP4 is the primary mediator of PGE2-driven inflammation. Its use in specific medical scenarios underscores its importance in the therapeutic landscape.

Metabolism:

Grapiprant undergoes metabolic processing primarily in: _In vitro_ studies with dog microsomes have reported the identification of four metabolites, an N-deamination metabolite which is the major metabolite in urine and feces, two hydroxylated metabolites and one N-oxidation metabolite. This metabolic pathway ensures efficient processing of the drug, helping to minimize potential toxicity and side effects.

Absorption:

The absorption characteristics of Grapiprant are crucial for its therapeutic efficacy: Studies in animals (horse) have shown the presence of a concentration >0.005 ng/ml in serum 72 hours after initial administration of a dose of 2 mg/kg. It is rapidly absorbed and the reported Cmax in this reports was 31.9 ng/ml in a Tmax of 1.5 hours and AUC of 2000 ng.hr/ml. In the case of bioavailability, grapiprant presents a mean bioavailability of 39%. The bioavailability, time for peak concentration and maximal concentration has been reported to be significantly reduced after food. The drug's ability to rapidly penetrate into cells ensures quick onset of action.

Half-life:

The half-life of Grapiprant is an important consideration for its dosing schedule: The reported elimination half-life in animal studies (horse) is of 5.86 hours. This determines the duration of action and helps in formulating effective dosing regimens.

Protein Binding:

Grapiprant exhibits a strong affinity for binding with plasma proteins: The serum protein binding of grapiprant was of about 95%. The main protein that binds to grapiprant is albumin. This property plays a key role in the drug's pharmacokinetics and distribution within the body.

Route of Elimination:

The elimination of Grapiprant from the body primarily occurs through: Following an oral dose, the majority of the dose an within the first 72 hours. Studies in animals (horse) have shown the presence of a concentration >0.005 ng/ml in urine 96 hours after initial administration of a dose of 2 mg/kg. From the excreted dose, 55%, 15% and 19% of the administered dose is excreted in bile, urine, and feces respectively. Understanding this pathway is essential for assessing potential drug accumulation and toxicity risks.

Volume of Distribution:

Grapiprant is distributed throughout the body with a volume of distribution of: The reported volume of distribution in animal studies (cats) was reported to be 918 ml/kg. This metric indicates how extensively the drug permeates into body tissues.

Clearance:

The clearance rate of Grapiprant is a critical factor in determining its safe and effective dosage: The reported clearance rate in animal studies (cats) was reported to be 173.2 ml/hr.kg. It reflects the efficiency with which the drug is removed from the systemic circulation.

Pharmacodynamics:

Grapiprant exerts its therapeutic effects through: Preclinical studies have shown that grapiprant is very effective to reduce acute and chronic pain and inflammation. The effect of grapiprant seems to be dose-dependent and it is comparable to the effect of rofecoxib and piroxicam. The effects of grapiprant have been reported to be effective in the relief from arthritic pain in canine patients. The drug's ability to modulate various physiological processes underscores its efficacy in treating specific conditions.

Mechanism of Action:

Grapiprant functions by: Grapiprant is an EP4 prostaglandin receptor antagonist and thus the activity of this drug is thought to be completely related to the selective blockade of this receptor. It binds to human and other mammals EP4 prostaglandin receptor with high affinity without interfering with other prostaglandin pathways which are important for a variety of physiological functions. The binding of grapiprant blocks PGE2 binding and hence its biological effect related to the signaling pain and inflammation cascade. Grapiprant has been accepted very greatly in veterinary as its mechanism of action is a targeted approach to pain management by not having any interaction with the production of prostanoids and thus, by not interacting with other prostaglandin receptor pathways. This mechanism highlights the drug's role in inhibiting or promoting specific biological pathways, contributing to its therapeutic effects.

Toxicity:

Classification:

Grapiprant belongs to the class of organic compounds known as phenylimidazoles. These are polycyclic aromatic compounds containing a benzene ring linked to an imidazole ring through a CC or CN bond, classified under the direct parent group Phenylimidazoles. This compound is a part of the Organic compounds, falling under the Organoheterocyclic compounds superclass, and categorized within the Azoles class, specifically within the Imidazoles subclass.

Categories:

Grapiprant is categorized under the following therapeutic classes: Amides, P-glycoprotein substrates, Sulfones, Sulfur Compounds. These classifications highlight the drug's diverse therapeutic applications and its importance in treating various conditions.

Experimental Properties:

Further physical and chemical characteristics of Grapiprant include:

• Water Solubility: Insoluble
• Melting Point: >136 ºC (Grapiprant hydrochloride)
• logP: 4.56