Luhan Pharmachem Co., Ltd.

Luhan pharmachem Co., Ltd. supplies Aprepitant bulk active pharmaceutical ingredient (API) to the pharmaceutical industry. Our Aprepitant is manufactured by cGMP compliant facility. Welcome to contact us for further details including current DMF status for the product and up to date regulatory status of the manufacturing facility. We look forward to assisting you with your research and development projects.

What is aprepitant?

Aprepitant is an antiemetic chemical compound that belongs to a class of drugs called substance P antagonists (SPA). It mediates its effect by blocking the neurokinin 1 (NK1) receptor.

Aprepitant is manufactured by Merck & Co. under the brand name Emend for prevention of acute and delayed chemotherapy-induced nausea and vomiting (CINV) and for prevention of postoperative nausea and vomiting. It was approved by the FDA in 2003.

Aprepitant may also be useful in the treatment of cyclic vomiting syndrome & late-stage chemotherapy induced vomiting, sickness but there are few studies to date.

On January 2008, online the FDA approved fosaprepitant, an intravenous form of aprepitant, which is to be sold under the tradename Emend Injection in the US and as Ivemend in some other countries.

Mechanism of Action

Aprepitant is classified as an NK1antagonist because it blocks signals given off by NK1 receptors. This, therefore, decreases the likelihood of vomiting in patients. Emend is usually taken as a preventative for chemotherapy-induced nausea and vomiting, which is a serious side-effect experienced by over 80% of patients who undergo chemotherapy.

NK1 is a G protein-coupled receptor located in the central and peripheral nervous system. This receptor has a dominant ligand known as Substance P (SP). SP is aneuropeptide, composed of 11 amino acids, which sends impulses and messages from the brain. It is found in high concentrations in the vomiting center of the brain, and, when activated, it results in a vomiting reflex. In addition to this it also plays a key part in the transmission of pain impulses from the peripheral receptors to the central nervous system.

Aprepitant has been shown to inhibit both the acute and delayed emesis induced by cytotoxic chemotherapeutic drugs by blocking substance P landing on receptors in the brain’s neurons. Positron Emission Tomography (PET) studies, have demonstrated that aprepitant can cross the blood brain barrier and bind to NK1 receptors in the human brain. It has also been shown to increase the activity of the 5-HT3 receptor antagonists ondansetron and the corticosteroid dexamethasone, which are also used to prevent nausea and vomiting caused by chemotherapy.

Aprepitant is taken orally in the form of a capsule. Before clinical testing, a new class of therapeutic agent has to be characterized in terms of preclinical metabolism and excretion studies.

Average bioavailability is found to be around 60-65%. Aprepitant is metabolized primarily by CYP3A4 with minor metabolism by CYP1A2 and CYP2C19. Seven metabolites of aprepitant, which are only weakly active, have been identified in human plasma. As a moderate inhibitor of CYP3A4, aprepitant can increase plasma concentrations of co-administered medicinal products that are metabolized through CYP3A4. Specific interaction has been demonstrated with oxycodone, where aprepitant both increased the efficacy and worsened the side effects of oxycodone; however it is unclear whether this is due to CPY3A4 inhibition or through its NK-1 antagonist action. Following IV administration of a 14C-labeled prodrug of aprepitant (L-758298), which is converted rapidly and completely to aprepitant, approximately 57% of the total radioactivity is excreted in the urine and 45% in feces. No unchanged substance is excreted in urine.

One of the main features of aprepitant, and a major advantage it has over other chemotherapy-induced side-effect treatments, is its ability to selectively antagonize NK1receptors, while having very low affinity to other common receptors such as serotonin, dopamine, and corticosteroid. It is estimated that aprepitant is at least 3,000 times more selective to NK1 receptors compared to these other enzyme transporter, ion channels. The normal dosing of aprepitant given as 125 mg in the first day after chemotherapy and followed by 80 mg the following 2 days.

Disclaimer:

Information on this page is provided for general information purposes. You should not make a clinical treatment decision based on information contained in this page without consulting other references including the package insert of the drug, textbooks and where relevant, expert opinion. We cannot be held responsible for any errors you make in administering drugs mentioned on this page, nor for use of any erroneous information contained on this page.