Aprepitant

Molecular formula C23H21F7N4O3 Molecular weight 534.43 CAS Registry No 170729-80-3 

add to a 500 mg Bond Elut CIS SPE cartridge, wash with 6 mL water, elute with 3 mL MeOH. Evaporate the eluate to dryness under a stream of nitrogen, reconstitute the residue with 300 pL mobile phase, inject an aliquot. Alternatively, mix 50 pL plasma or brain homogenate with 5 ng IS and 100 pL MeCN, vortex, centrifuge at 3000 g for 10 min, inject a 5-25 pL aliquot of the supernatant. 

Mobile phase MeCN 10 mM ammonium acetate formic acid 55 45 0.1 Flow rate 1 Injection volume 5-25 

Detector MS, Sciex API III-I-, heated nebulizer interface, dwell time 450 ms, m/z 535 to 

Huskey, S.-E.W. Dean, B.J. Bakhtiar, R. Sanchez, R.I. Tattersall, F.D. Rycroft, W. Hargreaves, R. Watt, A.P. Chicchi, G.G. Keohane, C. Hora, D.F. Chiu, S.-H.L. Brain penetration of aprepitant, a substance P receptor antagonist, in ferrets, Drug Metah.Dispos., 2003, 31, 785-791. 

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Aprepitant, which inhibits the cytochrome P450 isoform, CYP3A4, is metabolised by it. As a result,... 

Aprepitant (Emend) 125 mg on day 1, 1 hour prior to Most common Fatigue, hiccups... 

Aprepitant is the first NK3 receptor antagonist antiemetic drug33 NKj receptors are present in the CTZ and GI tract and are involved... 

Keller, Martin, Stuart Montgomery, William Ball, Mary Morrison, Duane Snavely, Guanghan Liu, Richard Hargreaves, Jarmo Hietala, Christopher Lines, Katherine Beebe and Scott Reines, Lack of Efficacy of the Substance P (Neurokinini Receptor) Antagonist Aprepitant in the Treatment of Major Depressive Disorder , Biological Psychiatry 59 (2006) 216-23... 

NK1 agonist-mediated gerbil foot tapping model (ID50 = 0.33 mpk) [34]. Aprepitant (36), which contains seven fluorine atoms, was subsequently approved by the Food and Drug Administration (FDA) for the prevention of acute and delayed chemotherapy-induced nausea and vomiting. 

Aprepitant is the first approved member of this class of drugs and is indicated as part of a multiple drug regimen for prophylaxis of nausea and vomiting associated with high-dose cisplatin-based chemotherapy. 

Patients receiving chemotherapy that is classified as being of high emetic risk should receive a combination antiemetic regimen containing three drugs on the day of chemotherapy administration (day 1)—an SSRI plus dexamethasone plus aprepitant. 

High SSRI + dexamethasone + aprepitant Days 2 and 3 after chemotherapy ... 

Moderate Anthracydine + cyclophosphamide SSRI (as above) and Dexamethasone 12 mg po (with aprepitant) and Aprepitant 125 mg po Aprepitant 80 mg po days 2 and 3... 

Aprepitant, dexamethasone, or metoclopramide have demonstrated efficacy in preventing CINV, whereas the results with SSRIs are inconsistent. 

Aprepitant and dexamethasone can be used on the 2 days following administration of high emetic risk chemotherapy. 

Both enantiomers of l-[3,5-bis(trifluoromethyl)phenyl]ethan-2-ol are of importance in the pharmaceutical industry, and so considerable effort has been expended in their asymmetric synthesis. The (7 )-enantiomer is a building block for aprepitant, a neurokinin-1 (NK-1) antagonist used for the treatment of chemotherapy-induced nausea (Figure 1.11). ... 

Figure 1.11 Aprepitant and an (R)-1 [3,5-bis(trifluoromethyl)phenyl]ethan-2-ol intermediate...

Antiemetic Aprepitant, in combination with other antiemetic agents, is indicated for the prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of highly emetogenic cancer chemotherapy, including high-dose cisplatin. 

Dosage regimen Aprepitant is given for 3 days as part of a regimen that includes a corticosteroid and a 5-HT3 antagonist. The recommended dose of aprepitant is 125... 

Chronic continuous administration is not recommended. Aprepitant may be taken with or without food. 

Concomitant therapy The oral dexamethasone doses should be reduced by approximately 50% when coadministered with aprepitant. 

Pharmacology Aprepitant is a selective high-affinity antagonist of human substance... 

P/neurokinin 1 (NK ) receptors. Aprepitant has little or no affinity for serotonin... 

Studies show that aprepitant augments the antiemetic activity of the 5-HT3-receptor... 

Absorption -The mean absolute oral bioavailability of aprepitant is approximately 60% to 65% and the mean peak plasma concentration (Cmax) aprepitant occurred at approximately 4 hours (Tmax)-... 

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