Grapiprant

Grapiprant Uses, Dosage, Side Effects, Food Interaction and all others data.

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.

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.

Grapiprant
Uses
Dosage
Side Effect
Precautions
Interactions
Uses during Pregnancy
Uses during Breastfeeding
Accute Overdose
Food Interaction
Half Life
Volume of Distribution
Clearance
Interaction With other Medicine
Contradiction
Storage

Trade Name	Grapiprant
Generic	Grapiprant
Grapiprant Other Names	Grapiprant
Type
Formula	C₂₆H₂₉N₅O₃S
Weight	Average: 491.61 Monoisotopic: 491.199110988
Protein binding	The serum protein binding of grapiprant was of about 95%. The main protein that binds to grapiprant is albumin.
Groups	Investigational, Vet approved
Therapeutic Class
Manufacturer
Available Country
Last Updated:	September 19, 2023 at 7:00 am

Uses

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.

How Grapiprant works

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.

Toxicity

Safety studies have demonstrated an excellent safety profile and a wide safety margin. In animal studies, the results of the 2.5-12X overdose were observed as soft-formed or mucous feces, occasionally bloody and vomiting.

Volume of Distribution

The reported volume of distribution in animal studies (cats) was reported to be 918 ml/kg.

Elimination Route

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.[A49842]

Half Life

The reported elimination half-life in animal studies (horse) is of 5.86 hours.

Clearance

The reported clearance rate in animal studies (cats) was reported to be 173.2 ml/hr.kg.

Elimination Route

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.