An antagonist of substance P that blocks NK 1 receptors in the brainstem emetic center.
Blocks the emetic effects of substance P.
NK 1 inhibitors improve chemotherapy-induced emesis on the day of chemotherapy and during the 3-4 days after.
Given orally on day one at 125 mg and days 2-3 (80mg).
(Emend)-when given with 5-HT3 antagonists conveys increased antiemetic response.
Trade name Emend
Protein binding >95%.
Hepatic metabolism mostly CYP3A4- mediated, but some contributions by CYP2C19 & CYP1A2
Biological half-life 9-13 hours.
Excretion Urine 5%, feces 86%.
An antiemetic chemical compound that belongs to a class of drugs called substance P antagonists (SPA).
Mediates its effect by blocking the neurokinin 1 (NK1) receptor.
For prevention of acute and delayed chemotherapy-induced nausea and vomiting (CINV) and for prevention of postoperative nausea and vomiting.
Fosaprepitant, an intravenous form of aprepitant, is sold under the trade name Emend Injection.
A single dose of intravenous fosapreitant on day 1 of chemotherapy is comparable in efficacy to the standard 3 day oral aprepitant regimen.
Fosaprepitant is associated with substantial venous irritation, especially with doxorubicin based chemotherapy regimens.
An NK1 antagonist because it blocks signals given off by NK1 receptors, and decreases the likelihood of vomiting in patients.
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, and has a dominant ligand known as Substance P (SP).
SP is a neuropeptide, composed of 11 amino acids, which sends impulses and messages from the brain.
Substance P is found in high concentrations in the vomiting center of the brain, and, when activated, it results in a vomiting reflex.
Substance P also plays a key part in the transmission of pain impulses from the peripheral receptors to the central nervous system.
Inhibits both the acute and delayed emesis induced by cytotoxic chemotherapeutic drugs by blocking substance P landing on receptors in the brain’s neurons.
Can cross the blood brain barrier and bind to NK1 receptors in the human brain.
Increases of 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.
Seven metabolites which are only weakly active, have been identified.
As a moderate inhibitor of CYP3A4, aprepitant can increase plasma concentrations of co-administered drugs that are metabolized through CYP3A4.
One of the major advantage it has over other chemotherapy-induced side-effect treatments, is its ability to selectively antagonize NK1 receptors, while having very low affinity to other common receptors such as serotonin, dopamine, and corticosteroid.
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.
Cinvanti is the injectable emulsion therapy with a two minute IV infusion for the prevention of acute inflate chemotherapy induced nausea and vomiting.