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 Aprepitant

Aprepitant is a small molecule, high-affinity substance P antagonist (SPA) with antiemetic activity. Crossing the blood brain barrier, aprepitant binds selectively to the human substance P/neurokinin 1 receptor in the central nervous system (CNS), thereby inhibiting receptor binding of endogenous substance P and substance P-induced emesis. This agent has little or no affinity for serotonin type 3 (5-HT3), dopamine, and corticosteroid receptors. Check for active clinical trials or closed clinical trials using this agent. (NCI Thesaurus).

Aprepitant is a white to off-white crystalline solid, with a molecular weight of 534.43. It is practically insoluble in water. Aprepitant is sparingly soluble in ethanol and isopropyl acetate and slightly soluble in acetonitrile. Each capsule of EMEND for oral administration contains either 40 mg, 80 mg, or 125 mg of aprepitant and the following inactive ingredients: sucrose, microcrystalline cellulose, hydroxypropyl cellulose and sodium lauryl sulfate. The capsule shell excipients are gelatin, titanium dioxide, and may contain sodium lauryl sulfate and silicon dioxide. The 40-mg capsule shell also contains yellow ferric oxide, and the 125-mg capsule also contains red ferric oxide and yellow ferric oxide.

Mechanism of Action
Aprepitant is a selective high-affinity antagonist of human substance P/neurokinin 1 (NK1) receptors. Aprepitant has little or no affinity for serotonin (5-HT3), dopamine, and corticosteroid receptors, the targets of existing therapies for chemotherapy-induced nausea and vomiting (CINV) and postoperative nausea and vomiting (PONV). Aprepitant has been shown in animal models to inhibit emesis induced by cytotoxic chemotherapeutic agents, such as cisplatin, via central actions. Animal and human Positron Emission Tomography (PET) studies with aprepitant have shown that it crosses the blood brain barrier and occupies brain NK 1 receptors. Animal and human studies show that aprepitant augments the antiemetic activity of the 5-HT3 receptor antagonist ondansetron and the corticosteroid dexamethasone and inhibits both the acute and delayed phases of cisplatin-induced emesis.

According to http://en.wikipedia.org/wiki/Aprepitant, Aprepitant (Emend (US, EU)) 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 but there are few studies to date. On January 2008, 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.

Initial development

Acute or delayed CINV is an unpleasant side effect experienced by over 80% of patients who undergo initial and repeated highly emetogenic cancer chemotherapy, for example cisplatin. Throughout the 1990s a noticeable increase occurred in the number of diagnosed cancer patients undergoing chemotherapy and therefore experiencing CINV. As a result of this, towards the end of the decade initial research was conducted to try to develop a drug that eases the severity and decreases the likelihood of CINV, and after several years of research Merck & Co. successfully developed a drug known as Emend. The active substance of Emend is aprepitant, which is effective in helping to prevent CINV because it antagonizes the NK1 receptor. This receptor is located at the brain stem nuclei of the dorsal vagal complex and is a crucial part of the regulation of vomiting. This is due to the receptor binding with substance P, a peptide neurotransmitter. see  http://en.wikipedia.org/wiki/Aprepitan

Highlights on recent research using aprepitant

1. Aprepitant does not alter the pharmacokinetics of high-dose melphalan chemotherapy in patients with multiple myeloma.

AIMS: The objective of this investigation was to assess the effect of aprepitant on the pharmacokinetics of high-dose melphalan used as conditioning therapy before blood stem cell transplantation in multiple myeloma. METHODS: Aprepitant (125 mg) or placebo was administered 1 h before melphalan therapy (1 h infusion of 100 mg/m2). Eleven plasma samples were obtained over 8 h and melphalan was quantified using an LC/MS/MS method. Standard pharmacokinetic parameters were calculated and nonparametric testing was applied to assess the differences between aprepitant and placebo treatment.
RESULTS: Twenty patients received placebo and 10 patients aprepitant treatment. There were no differences observed for C(max) at the end of melphalan infusion (placebo 3431 +/- 608 ng/mL vs. aprepitant 3269 +/- 660 ng.mL). In addition, AUC and terminal elimination half-life were not changed by aprepitant. Total clearance of melphalan was 304 +/- 58 ml min-1 m-2 (placebo) which was not influenced by aprepitant (288 +/- 78 ml min-1 m-2). CONCLUSIONS: The administration of the NK1 receptor antagonist aprepitant 1 h before a high-dose chemotherapy does not influence the exposure and the elimination of melphalan. Therefore, oral administration of 125 mg aprepitant 1 h before melphalan infusion does not alter the disposition of intravenously administered melphalan. [source: Egerer G, Eisenlohr K, Gronkowski M, Burhenne J, Riedel KD, Mikus G. Br J Clin Pharmacol. 2010 Dec;70(6):903-7.]

2. Aprepitant use in children, adolescents, and young adults for the control of chemotherapy-induced nausea and vomiting (CINV).

BACKGROUND: One of the most common and distressing side effects for cancer patients is chemotherapy-induced nausea and vomiting (CINV). New antiemetics, such as the NK-1 receptor inhibitor aprepitant, have been reported to improve control of this side effect in adults. However, little is known about its effect in the pediatric oncology population, with only a few reported cases in the literature. CONCLUSIONS: Aprepitant when combined with standard antiemetics, was well tolerated in the pediatric oncology population studied. However, there is still a need to conduct prospective studies to determine the optimal efficacy of aprepitant in the pediatric oncology population. [source: Choi MR, Jiles C, Seibel NL. J Pediatr Hematol Oncol. 2010 Oct;32(7):e268-71.]

3. Aprepitant: a review of its use in the prevention of nausea and vomiting.

Aprepitant (Emend) is a neurokinin-1 (NK(1)) receptor antagonist that is able to alleviate the emetic effects of substance P. When combined with a standard regimen of a corticosteroid (dexamethasone) and a serotonin 5-HT(3) receptor antagonist (ondansetron), oral aprepitant (125 mg on day 1 then 80 mg once daily on days 2 and 3) was effective in the prevention of acute and delayed chemotherapy-induced nausea and vomiting (CINV) associated with single or multiple cycles of highly emetogenic chemotherapy (HEC). This aprepitant regimen was also effective in the prevention of CINV in patients treated with single or multiple cycles of moderately emetogenic chemotherapy (MEC). A single oral dose of aprepitant 40 mg administered prior to patients undergoing abdominal surgery was also effective in the prevention of postoperative nausea and vomiting (PONV). Aprepitant was generally well tolerated. Aprepitant is a recommended option for the treatment of PONV, and when combined with a corticosteroid and 5-HT(3) receptor antagonist is a recommended regimen for the treatment of CINV. [source: Curran MP, Robinson DM. Drugs. 2009;69(13):1853-78.]

4. Aprepitant- in the control of chemotherapy-induced nausea and vomiting

Despite progress in the area of supportive care in oncology in the last two decades, nausea and vomiting continue to be significant side effects of cancer therapy. These symptoms can escalate over time and can result in patients' refusal to continue with chemotherapy. Introduction of serotonin (5-HT3) receptor antagonists was a major therapeutic advance in the treatment of chemotherapy-induced nausea and vomiting with enhanced efficacy when corticosteroids were added. However, these agents have limited protection in the acute phase of chemotherapy-induced nausea and vomiting with little or no effect over the delayed phase. The aim of this review was to introduce a new class of antiemetics, a selective high-affinity antagonist at human substance P neurokinin 1 (NK(1)) receptors-aprepitant. Its pharmacological characteristics as well as its efficacy are reviewed. Aprepitant appears to be well tolerated but, due to its inhibitory effect on cytochrome P450 isoenzyme 3A4, it can lead to significant drug interactions, resulting in need for dose modification of concomitant therapy. The addition of aprepitant to 5-HT(3) receptor antagonists and corticosteroids was found to be superior to the combination of 5-HT(3) receptor antagonists and corticosteroids alone in patients treated with highly and moderately emetogenic chemotherapy. Clinical trials with aprepitant and other antiemetic agents are warranted to determine a regimen that will ensure complete protection from both acute and delayed chemotherapy-induced nausea and vomiting, thus contributing to improved supportive care and patients' quality of life (QoL). [source: Sarcev T, Secen N, Zaric B, Milovancev A. J BUON. 2008 Jul-Sep;13(3):333-9.]

5. Nanomedicines in the treatment of emesis during chemotherapy: focus on aprepitant.

Aprepitant, a selective high-affinity antagonist of human substance P/neurokinin 1 (NK1) receptors, is the active ingredient of EMEND which has recently been approved by the FDA for the prevention of chemotherapy-induced nausea and vomiting (CINV). Aprepitant undergoes extensive metabolism, primarily via CYP3A4 mediated oxidation. It is eliminated primarily by metabolism and is not renally excreted. The apparent terminal half-life in humans ranged from 9 to 13 hours. Early development studies led to the development of a nanoparticle formulation to enhance exposure and minimize food effects. Two large randomized trials accruing 1099 patients studied the effect in patients receiving cisplatin of adding aprepitant to ondansetron and dexamethasone on day 1 then to dexamethasone on days 2 and 3 to control delayed emesis. The complete response of no vomiting and no rescue medication overall from days 1 to 5 improved from 48% to 68% (p<0.001), a 13% improvement in acute emesis but a 21% improvement in delayed emesis with the improvement from 51% to 72% (p<0.001). Similarly, 866 patients treated with cyclophosphamide plus either doxorubicin or epirubicin, received either ondansetron, dexamethasone, and aprepitant on day 1 followed by aprepitant on days 2 and 3 or ondansetron and dexamethasone on day 1 and dexamethasone on days 2 and 3. The overall complete response rate over 5 days was better for the aprepitant group 50.8% vs 42.5% (p=0.015). Complete responses were reported in more patients taking aprepitant in both the acute (76% vs 69%, p=0.034) and delayed (55% vs 49%, p=0.064) phases of vomiting. There were no clinically relevant differences in toxicity by adding aprepitant and improvements in the quality of life of patients on chemotherapy were recorded. [source: Olver I, Shelukar S, Thompson KC. Int J Nanomedicine. 2007;2(1):13-8.]

 1: Gerber PA, Buhren BA, Homey B. More on aprepitant for erlotinib-induced pruritus. N Engl J Med. 2011 Feb 3;364(5):486-7. PubMed PMID: 21288112.

2: Mir O, Blanchet B, Goldwasser F. More on aprepitant for erlotinib-induced pruritus. N Engl J Med. 2011 Feb 3;364(5):487. PubMed PMID: 21288111.

3: Egerer G, Eisenlohr K, Gronkowski M, Burhenne J, Riedel KD, Mikus G. The NK₁ receptor antagonist aprepitant does not alter the pharmacokinetics of high-dose melphalan chemotherapy in patients with multiple myeloma. Br J Clin Pharmacol. 2010 Dec;70(6):903-7. doi: 10.1111/j.1365-2125.2010.03792.x. PubMed PMID: 21175446; PubMed Central PMCID: PMC3014074.

4: Fang ZW, Zhai SD. [A meta-analysis of aprepitant for prevention of chemotherapy-induced nausea and vomiting]. Beijing Da Xue Xue Bao. 2010 Dec 18;42(6):756-63. Chinese. PubMed PMID: 21170111.

5: Abe T, Hachiro Y, Kunimoto M. [Clinical usefulness of oral aprepitant for alleviation of delayed nausea and vomiting induced by mFOLFOX6--report of a case]. Gan To Kagaku Ryoho. 2010 Dec;37(13):2933-5. Japanese. PubMed PMID: 21160274.

6: Takahashi T, Nakamura Y, Tsuya A, Murakami H, Endo M, Yamamoto N. Pharmacokinetics of aprepitant and dexamethasone after administration of chemotherapeutic agents and effects of plasma substance P concentration on chemotherapy-induced nausea and vomiting in Japanese cancer patients. Cancer Chemother Pharmacol. 2010 Dec 2. [Epub ahead of print] PubMed PMID: 21125277.

7: Muñoz M, González-Ortega A, Coveñas R. The NK-1 receptor is expressed in human leukemia and is involved in the antitumor action of aprepitant and other NK-1 receptor antagonists on acute lymphoblastic leukemia cell lines. Invest New Drugs. 2010 Dec 1. [Epub ahead of print] PubMed PMID: 21120581.

8: Habib AS, Keifer JC, Borel CO, White WD, Gan TJ. A Comparison of the Combination of Aprepitant and Dexamethasone Versus the Combination of Ondansetron and Dexamethasone for the Prevention of Postoperative Nausea and Vomiting in Patients Undergoing Craniotomy. Anesth Analg. 2010 Nov 16. [Epub ahead of print] PubMed PMID: 21081776.

9: Kast RE. Glioblastoma: synergy of growth promotion between CCL5 and NK-1R can be thwarted by blocking CCL5 with miraviroc, an FDA approved anti-HIV drug and blocking NK-1R with aprepitant, an FDA approved anti-nausea drug. J Clin Pharm Ther. 2010 Dec;35(6):657-63. doi: 10.1111/j.1365-2710.2009.01148.x. PubMed PMID: 21054456.

10: Langford P, Chrisp P. Fosaprepitant and aprepitant: an update of the evidence for their place in the prevention of chemotherapy-induced nausea and vomiting. Core Evid. 2010 Oct 21;5:77-90. PubMed PMID: 21042544; PubMed Central PMCID: PMC2963924.

11: Booken N, Heck M, Nicolay JP, Klemke CD, Goerdt S, Utikal J. Oral aprepitant in the therapy of refractory pruritus in erythrodermic cutaneous T-cell lymphoma. Br J Dermatol. 2010 Oct 29. doi: 10.1111/j.1365-2133.2010.10108.x. [Epub ahead of print] PubMed PMID: 21039410.

12: Manak MM, Moshkoff DA, Nguyen LT, Meshki J, Tebas P, Tuluc F, Douglas SD. Anti-HIV-1 activity of the neurokinin-1 receptor antagonist aprepitant and synergistic interactions with other antiretrovirals. AIDS. 2010 Nov 27;24(18):2789-96. PubMed PMID: 20975512.

13: Levêque D. Aprepitant for erlotinib-induced pruritus. N Engl J Med. 2010 Oct 21;363(17):1680-1; author reply 1681. PubMed PMID: 20961258.

14: Jordan K, Jahn F, Jahn P, Behlendorf T, Stein A, Ruessel J, Kegel T, Schmoll HJ. The NK-1 receptor-antagonist aprepitant in high-dose (HD) chemotherapy (HD melphalan and HD T-ICE: paclitaxel, ifosfamide, carboplatin, etoposide): efficacy and safety of a triple antiemetic combination. Bone Marrow Transplant. 2010 Sep 13. [Epub ahead of print] PubMed PMID: 20838387.

15: Choi MR, Jiles C, Seibel NL. Aprepitant use in children, adolescents, and young adults for the control of chemotherapy-induced nausea and vomiting (CINV). J Pediatr Hematol Oncol. 2010 Oct;32(7):e268-71. PubMed PMID: 20736848.

16: Stoch SA, Gargano C, Valentine J, Braun MP, Murphy MG, Fedgchin M, Majumdar A, Pequignot E, Gottesdiener KM, Petty KJ, Panebianco D, Dean D, Kraft WK, Greenberg HE. Double-blind crossover study to assess potential differences in cytochrome P450 3A4 activity in healthy subjects receiving ondansetron plus dexamethasone, with and without aprepitant. Cancer Chemother Pharmacol. 2010 Aug 24. [Epub ahead of print] PubMed PMID: 20734049.

17: Takahashi T, Hoshi E, Takagi M, Katsumata N, Kawahara M, Eguchi K. Multicenter, phase II, placebo-controlled, double-blind, randomized study of aprepitant in Japanese patients receiving high-dose cisplatin. Cancer Sci. 2010 Nov;101(11):2455-61. doi: 10.1111/j.1349-7006.2010.01689.x. PubMed PMID: 20718754.

18: Vincenzi B, Tonini G, Santini D. Aprepitant for erlotinib-induced pruritus. N Engl J Med. 2010 Jul 22;363(4):397-8. PubMed PMID: 20660413.

19: Shono Y, Jantratid E, Kesisoglou F, Reppas C, Dressman JB. Forecasting in vivo oral absorption and food effect of micronized and nanosized aprepitant formulations in humans. Eur J Pharm Biopharm. 2010 Sep;76(1):95-104. Epub 2010 Jun 1. PubMed PMID: 20576487.

20: Longo F, Mansueto G, Lapadula V, De Sanctis R, Quadrini S, Grande R, Gori B, Altavilla A, D'Antoni I, Del Signore E, Stumbo L, De Luca C, Cimadon B, Cortesi E, Gamucci T, Di Seri M. Palonosetron plus 3-day aprepitant and dexamethasone to prevent nausea and vomiting in patients receiving highly emetogenic chemotherapy. Support Care Cancer. 2010 Jun 16. [Epub ahead of print] PubMed PMID: 20552375.

21: Vincenzi B, Fratto ME, Santini D, Tonini G. Aprepitant against pruritus in patients with solid tumours. Support Care Cancer. 2010 Sep;18(9):1229-30. Epub 2010 Jun 11. PubMed PMID: 20544226.

22: Ständer S, Siepmann D, Herrgott I, Sunderkötter C, Luger TA. Targeting the neurokinin receptor 1 with aprepitant: a novel antipruritic strategy. PLoS One. 2010 Jun 4;5(6):e10968. PubMed PMID: 20532044; PubMed Central PMCID: PMC2881044.

23: Paiva CE, Paiva BS, Michelin OC. Does neurokinin-1-receptor antagonist aprepitant diminish the efficacy of cyclophosphamide-based chemotherapy? Sao Paulo Med J. 2009 Nov;127(6):385-6. PubMed PMID: 20512296.

24: Aapro MS, Walko CM. Aprepitant: drug-drug interactions in perspective. Ann Oncol. 2010 Dec;21(12):2316-23. Epub 2010 May 20. PubMed PMID: 20488873.

25: Millan MJ, Dekeyne A, Gobert A, Mannoury la Cour C, Brocco M, Rivet JM, Di Cara B, Lejeune F, Cremers TI, Flik G, de Jong TR, Olivier B, de Nanteuil G. S41744, a dual neurokinin (NK)1 receptor antagonist and serotonin (5-HT) reuptake inhibitor with potential antidepressant properties: a comparison to aprepitant (MK869) and paroxetine. Eur Neuropsychopharmacol. 2010 Sep;20(9):599-621. Epub 2010 May 18. PubMed PMID: 20483567.

26: Warr DG, Street JC, Carides AD. Evaluation of risk factors predictive of nausea and vomiting with current standard-of-care antiemetic treatment: analysis of phase 3 trial of aprepitant in patients receiving adriamycin-cyclophosphamide-based chemotherapy. Support Care Cancer. 2010 May 13. [Epub ahead of print] PubMed PMID: 20461438.

27: Muñoz M, Rosso M, Robles-Frias MJ, Salinas-Martín MV, Rosso R, González-Ortega A, Coveñas R. The NK-1 receptor is expressed in human melanoma and is involved in the antitumor action of the NK-1 receptor antagonist aprepitant on melanoma cell lines. Lab Invest. 2010 Aug;90(8):1259-69. Epub 2010 May 10. PubMed PMID: 20458280.

28: DiIorio TM, Sharkey PF, Hewitt AM, Parvizi J. Antiemesis after total joint arthroplasty: does a single preoperative dose of aprepitant reduce nausea and vomiting? Clin Orthop Relat Res. 2010 Sep;468(9):2405-9. PubMed PMID: 20419358; PubMed Central PMCID: PMC2919891.

29: Hartrick CT, Tang YS, Hunstad D, Pappas J, Muir K, Pestano C, Silvasi D. Aprepitant vs. multimodal prophylaxis in the prevention of nausea and vomiting following extended-release epidural morphine. Pain Pract. 2010 May-Jun;10(3):245-8. Epub 2010 Mar 2. PubMed PMID: 20230453.

30: Sankhala KK, Pandya DM, Sarantopoulos J, Soefje SA, Giles FJ, Chawla SP. Prevention of chemotherapy induced nausea and vomiting: a focus on aprepitant. Expert Opin Drug Metab Toxicol. 2009 Dec;5(12):1607-14. Review. PubMed PMID: 19929449.

31: Duval A, Dubertret L. Aprepitant as an antipruritic agent? N Engl J Med. 2009 Oct 1;361(14):1415-6. PubMed PMID: 19797294.

32: Hansen Ho, Yuen C. Aprepitant-associated ifosfamide neurotoxicity. J Oncol Pharm Pract. 2010 Jun;16(2):137-8. Epub 2009 Sep 16. PubMed PMID: 19759053.

33: Hesketh PJ, Aapro M, Street JC, Carides AD. Evaluation of risk factors predictive of nausea and vomiting with current standard-of-care antiemetic treatment: analysis of two phase III trials of aprepitant in patients receiving cisplatin-based chemotherapy. Support Care Cancer. 2010 Sep;18(9):1171-7. Epub 2009 Sep 12. PubMed PMID: 19756774.

34: Curran MP, Robinson DM. Aprepitant: a review of its use in the prevention of nausea and vomiting. Drugs. 2009;69(13):1853-78. doi: 10.2165/11203680-000000000-00000. Review. PubMed PMID: 19719336.

35: Marbury TC, Jin B, Panebianco D, Murphy MG, Sun H, Evans JK, Han TH, Constanzer ML, Dru J, Shadle CR. Lack of effect of aprepitant or its prodrug fosaprepitant on QTc intervals in healthy subjects. Anesth Analg. 2009 Aug;109(2):418-25. PubMed PMID: 19608812.

36: Kast RE. Why cerebellar glioblastoma is rare and how that indicates adjunctive use of the FDA-approved anti-emetic aprepitant might retard cerebral glioblastoma growth: a new hypothesis to an old question. Clin Transl Oncol. 2009 Jul;11(7):408-10. PubMed PMID: 19574198.

37: Rapoport BL, Jordan K, Boice JA, Taylor A, Brown C, Hardwick JS, Carides A, Webb T, Schmoll HJ. Aprepitant for the prevention of chemotherapy-induced nausea and vomiting associated with a broad range of moderately emetogenic chemotherapies and tumor types: a randomized, double-blind study. Support Care Cancer. 2010 Apr;18(4):423-31. Epub 2009 Jul 1. PubMed PMID: 19568773.

38: Paul B, Trovato JA, Thompson J, Badros AZ, Goloubeva O. Efficacy of aprepitant in patients receiving high-dose chemotherapy with hematopoietic stem cell support. J Oncol Pharm Pract. 2010 Mar;16(1):45-51. Epub 2009 Jun 12. PubMed PMID: 19525301.

39: Shiu JR, Romanick M, Stobart K. Aprepitant for the prevention of chemotherapy-induced nausea and vomiting in adolescents. Pediatr Blood Cancer. 2009 Dec 15;53(7):1357; author reply 1358. PubMed PMID: 19492324.

40: Chong K, Dhatariya K. A case of severe, refractory diabetic gastroparesis managed by prolonged use of aprepitant. Nat Rev Endocrinol. 2009 May;5(5):285-8. Erratum in: Nat Rev Endocrinol. 2009 Jun;5(6):293. Dosage error in article text. PubMed PMID: 19444262.

41: Hache JJ, Vallejo MC, Waters JH, Williams BA. Aprepitant in a multimodal approach for prevention of postoperative nausea and vomiting in high-risk patients: is there such a thing as "too many modalities"? ScientificWorldJournal. 2009 Apr 28;9:291-9. PubMed PMID: 19412558.

42: Pikó B; Hungarian College of Oncology and Radiotherapy, Section of Financing. [Position statement of the (Hungarian) College of Oncology and Radiotherapy regarding the health insurance reimbursement for Emend(aprepitant)]. Magy Onkol. 2009 Mar;53(1):81-2. Hungarian. PubMed PMID: 19318331.

43: Galy G, Labidi SI, Tissier F, Combes JD, Auger A, Favier B, Latour JF. [Aprepitant for the prevention of cisplatine induced nausea and vomiting: an observational study]. Bull Cancer. 2009 Feb;96(2):141-5. French. PubMed PMID: 19258220.

44: Abbrederis K, Lorenzen S, Rothling N, Ihbe-Heffinger A, Schuster T, Peschel C, Lordick F. Chemotherapy-induced nausea and vomiting in the treatment of gastrointestinal tumors and secondary prophylaxis with aprepitant. Onkologie. 2009 Feb;32(1-2):30-4. Epub 2009 Jan 20. PubMed PMID: 19209016.

45: Wu D, Paul DJ, Zhao X, Douglas SD, Barrett JS. A sensitive and rapid liquid chromatography-tandem mass spectrometry method for the quantification of the novel neurokinin-1 receptor antagonist aprepitant in rhesus macaque plasma, and cerebral spinal fluid, and human plasma with application in translational NeuroAIDs research. J Pharm Biomed Anal. 2009 Apr 5;49(3):739-45. Epub 2008 Dec 13. PubMed PMID: 19167182; PubMed Central PMCID: PMC2883891.

46: Gray H. Aprepitant for postoperative nausea and vomiting. Anaesth Intensive Care. 2009 Jan;37(1):135-6. PubMed PMID: 19157363.

47: Muñoz M, Rosso M. The NK-1 receptor antagonist aprepitant as a broad spectrum antitumor drug. Invest New Drugs. 2010 Apr;28(2):187-93. Epub 2009 Jan 17. PubMed PMID: 19148578.

48: Jordan K, Kinitz I, Voigt W, Behlendorf T, Wolf HH, Schmoll HJ. Safety and efficacy of a triple antiemetic combination with the NK-1 antagonist aprepitant in highly and moderately emetogenic multiple-day chemotherapy. Eur J Cancer. 2009 May;45(7):1184-7. Epub 2009 Jan 8. PubMed PMID: 19135359.

49: Hesketh PJ, Younger J, Sanz-Altamira P, Hayden M, Bushey J, Trainor B, Krentzin M, Nowd P, Arnaoutakis K, Hesketh AM. Aprepitant as salvage antiemetic therapy in breast cancer patients receiving doxorubicin and cyclophosphamide. Support Care Cancer. 2008 Dec 6. [Epub ahead of print] PubMed PMID: 19066985.

50: Dupuis LL, Lingertat-Walsh K, Walker SE. Stability of an extemporaneous oral liquid aprepitant formulation. Support Care Cancer. 2009 Jun;17(6):701-6. Epub 2008 Nov 29. PubMed PMID: 19043742.

51: Grunberg SM, Dugan M, Muss H, Wood M, Burdette-Radoux S, Weisberg T, Siebel M. Effectiveness of a single-day three-drug regimen of dexamethasone, palonosetron, and aprepitant for the prevention of acute and delayed nausea and vomiting caused by moderately emetogenic chemotherapy. Support Care Cancer. 2009 May;17(5):589-94. Epub 2008 Nov 27. PubMed PMID: 19037667.

52: Jarkowski A 3rd. Possible contribution of aprepitant to ifosfamide-induced neurotoxicity. Am J Health Syst Pharm. 2008 Dec 1;65(23):2229-31. PubMed PMID: 19020190.

53: Gore L, Chawla S, Petrilli A, Hemenway M, Schissel D, Chua V, Carides AD, Taylor A, Devandry S, Valentine J, Evans JK, Oxenius B; Adolescent Aprepitant in Cancer Study Group. Aprepitant in adolescent patients for prevention of chemotherapy-induced nausea and vomiting: a randomized, double-blind, placebo-controlled study of efficacy and tolerability. Pediatr Blood Cancer. 2009 Feb;52(2):242-7. PubMed PMID: 18985740.

54: Sarcev T, Secen N, Zaric B, Milovancev A. Aprepitant--where do we stand in the control of chemotherapy-induced nausea and vomiting? J BUON. 2008 Jul-Sep;13(3):333-9. Review. PubMed PMID: 18979546.

55: Howell JE, Szabatura AH, Hatfield Seung A, Nesbit SA. Characterization of the occurrence of ifosfamide-induced neurotoxicity with concomitant aprepitant. J Oncol Pharm Pract. 2008 Sep;14(3):157-62. PubMed PMID: 18719071.

56: Wang X, Douglas SD, Song L, Wang YJ, Ho WZ. Neurokinin-1 receptor antagonist (aprepitant) suppresses HIV-1 infection of microglia/macrophages. J Neuroimmune Pharmacol. 2008 Dec;3(4):257-64. Epub 2008 Jul 25. PubMed PMID: 18654860; PubMed Central PMCID: PMC2675876.

57: Tamási L, Müller V, Magyar P. [Experience with aprepitant in the prevention of nausea and vomiting caused by highly emetic chemotherapy of lung cancer]. Magy Onkol. 2008 Jun;52(2):179-83. Hungarian. PubMed PMID: 18640894.

58: Bardia A, Thompson S, Atherton PJ, Barton DL, Sloan JA, Kottschade LA, Christensen B, Collins M, Loprinzi CL. Pilot evaluation of aprepitant for the treatment of hot flashes. Support Cancer Ther. 2006 Jul 1;3(4):240-6. PubMed PMID: 18632500.

59: Ibrahim RB, Abidi MH, Ayash LJ, Cronin SM, Cadotte C, Mulawa J, Jacobson PA, Smith DW, Uberti JP, Edwards DJ. Effect of aprepitant on intravenous tacrolimus disposition in reduced intensity hematopoietic stem cell transplantation. J Oncol Pharm Pract. 2008 Sep;14(3):113-21. Epub 2008 Jun 13. Erratum in: J Oncol Pharm Pract. 2008 Dec;14(4):233. PubMed PMID: 18556719.

60: Herrington JD, Jaskiewicz AD, Song J. Randomized, placebo-controlled, pilot study evaluating aprepitant single dose plus palonosetron and dexamethasone for the prevention of acute and delayed chemotherapy-induced nausea and vomiting. Cancer. 2008 May 1;112(9):2080-7. PubMed PMID: 18327813.

61: Yeo W, Mo FK, Suen JJ, Ho WM, Chan SL, Lau W, Koh J, Yeung WK, Kwan WH, Lee KK, Mok TS, Poon AN, Lam KC, Hui EK, Zee B. A randomized study of aprepitant, ondansetron and dexamethasone for chemotherapy-induced nausea and vomiting in Chinese breast cancer patients receiving moderately emetogenic chemotherapy. Breast Cancer Res Treat. 2009 Feb;113(3):529-35. Epub 2008 Mar 10. PubMed PMID: 18327706.

62: Nakade S, Ohno T, Kitagawa J, Hashimoto Y, Katayama M, Awata H, Kodama Y, Miyata Y. Population pharmacokinetics of aprepitant and dexamethasone in the prevention of chemotherapy-induced nausea and vomiting. Cancer Chemother Pharmacol. 2008 Dec;63(1):75-83. Epub 2008 Mar 4. PubMed PMID: 18317761.

63: Madsen JL, Fuglsang S. A randomized, placebo-controlled, crossover, double-blind trial of the NK1 receptor antagonist aprepitant on gastrointestinal motor function in healthy humans. Aliment Pharmacol Ther. 2008 Apr 1;27(7):609-15. Epub 2008 Jan 16. PubMed PMID: 18208572.

64: Wang X, Douglas SD, Lai JP, Tuluc F, Tebas P, Ho WZ. Neurokinin-1 receptor antagonist (aprepitant) inhibits drug-resistant HIV-1 infection of macrophages in vitro. J Neuroimmune Pharmacol. 2007 Mar;2(1):42-8. Epub 2007 Jan 12. PubMed PMID: 18040825.

65: Carides A, Reiss T, Lines C, McKeon B, Diemunsch P. Comparisons of aprepitant and ondansetron. Am J Health Syst Pharm. 2007 Dec 1;64(23):2422-4; author reply 2424-6. PubMed PMID: 18029945.

66: Annemans L, Strens D, Lox E, Petit C, Malonne H. Cost-effectiveness analysis of aprepitant in the prevention of chemotherapy-induced nausea and vomiting in Belgium. Support Care Cancer. 2008 Aug;16(8):905-15. Epub 2007 Oct 27. PubMed PMID: 17965891.

67: Diemunsch P, Apfel C, Gan TJ, Candiotti K, Philip BK, Chelly J, Carides AD, Evans JK, Ho TW, Reiss T. Preventing postoperative nausea and vomiting: post hoc analysis of pooled data from two randomized active-controlled trials of aprepitant. Curr Med Res Opin. 2007 Oct;23(10):2559-65. PubMed PMID: 17845742.

68: Olver I, Shelukar S, Thompson KC. Nanomedicines in the treatment of emesis during chemotherapy: focus on aprepitant. Int J Nanomedicine. 2007;2(1):13-8. Review. PubMed PMID: 17722507; PubMed Central PMCID: PMC2673828.

69: Nieber K, Schoppmeyer K. [Prevention of nausea and vomiting. Aprepitant, the first therapeutic acting NK-1 receptor antagonist]. Pharm Unserer Zeit. 2007;36(5):373-80. Review. German. PubMed PMID: 17722144.

70: Rodgers J, Bradley B, Kennedy PG. Combination chemotherapy with a substance P receptor antagonist (aprepitant) and melarsoprol in a mouse model of human African trypanosomiasis. Parasitol Int. 2007 Dec;56(4):321-4. Epub 2007 Jun 29. PubMed PMID: 17643344.

71: Diemunsch P, Gan TJ, Philip BK, Girao MJ, Eberhart L, Irwin MG, Pueyo J, Chelly JE, Carides AD, Reiss T, Evans JK, Lawson FC; Aprepitant-PONV Protocol 091 International Study Group. Single-dose aprepitant vs ondansetron for the prevention of postoperative nausea and vomiting: a randomized, double-blind phase III trial in patients undergoing open abdominal surgery. Br J Anaesth. 2007 Aug;99(2):202-11. Epub 2007 May 30. PubMed PMID: 17540667.

72: Lasseter KC, Gambale J, Jin B, Bergman A, Constanzer M, Dru J, Han TH, Majumdar A, Evans JK, Murphy MG. Tolerability of fosaprepitant and bioequivalency to aprepitant in healthy subjects. J Clin Pharmacol. 2007 Jul;47(7):834-40. Epub 2007 May 24. PubMed PMID: 17525168.

73: Majumdar AK, Yan KX, Selverian DV, Barlas S, Constanzer M, Dru J, McCrea JB, Ahmed T, Frick GS, Kraft WK, Petty KJ, Greenberg HE. Effect of aprepitant on the pharmacokinetics of intravenous midazolam. J Clin Pharmacol. 2007 Jun;47(6):744-50. Epub 2007 Apr 26. PubMed PMID: 17463213.

74: Gan TJ, Apfel CC, Kovac A, Philip BK, Singla N, Minkowitz H, Habib AS, Knighton J, Carides AD, Zhang H, Horgan KJ, Evans JK, Lawson FC; Aprepitant-PONV Study Group. A randomized, double-blind comparison of the NK1 antagonist, aprepitant, versus ondansetron for the prevention of postoperative nausea and vomiting. Anesth Analg. 2007 May;104(5):1082-9, tables of contents. PubMed PMID: 17456656.

75: Girish C, Manikandan S. Aprepitant: a substance P antagonist for chemotherapy induced nausea and vomiting. Indian J Cancer. 2007 Jan-Mar;44(1):25-30. Review. PubMed PMID: 17401221.

76: Durand JP, Gourmel B, Mir O, Goldwasser F. Antiemetic neurokinin-1 antagonist aprepitant and ifosfamide-induced encephalopathy. Ann Oncol. 2007 Apr;18(4):808-9. PubMed PMID: 17389531.

77: Osorio-Sanchez JA, Karapetis C, Koczwara B. Efficacy of aprepitant in management of chemotherapy-induced nausea and vomiting. Intern Med J. 2007 Apr;37(4):247-50. PubMed PMID: 17388865.

78: Cavaretta M, Noviasky J. Study flaw in comparisons of aprepitant and ondansetron. Am J Health Syst Pharm. 2007 Feb 15;64(4):350. PubMed PMID: 17299172.

79: Moore S, Tumeh J, Wojtanowski S, Flowers C. Cost-effectiveness of aprepitant for the prevention of chemotherapy-induced nausea and vomiting associated with highly emetogenic chemotherapy. Value Health. 2007 Jan-Feb;10(1):23-31. PubMed PMID: 17261113.

80: Chizh BA, Göhring M, Tröster A, Quartey GK, Schmelz M, Koppert W. Effects of oral pregabalin and aprepitant on pain and central sensitization in the electrical hyperalgesia model in human volunteers. Br J Anaesth. 2007 Feb;98(2):246-54. PubMed PMID: 17251214.

81: Oechsle K, Müller MR, Hartmann JT, Kanz L, Bokemeyer C. Aprepitant as salvage therapy in patients with chemotherapy-induced nausea and emesis refractory to prophylaxis with 5-HT(3) antagonists and dexamethasone. Onkologie. 2006 Dec;29(12):557-61. Epub 2006 Dec 11. PubMed PMID: 17202825.

82: Chrisp P. Aprepitant: the evidence for its place in the prevention of chemotherapy-induced nausea and vomiting. Core Evid. 2007 Mar 31;2(1):15-30. PubMed PMID: 21221195; PubMed Central PMCID: PMC3012554.

83: Lordick F, Ehlken B, Ihbe-Heffinger A, Berger K, Krobot KJ, Pellissier J, Davies G, Deuson R. Health outcomes and cost-effectiveness of aprepitant in outpatients receiving antiemetic prophylaxis for highly emetogenic chemotherapy in Germany. Eur J Cancer. 2007 Jan;43(2):299-307. Epub 2006 Nov 28. PubMed PMID: 17134890.

84: Loos WJ, de Wit R, Freedman SJ, Van Dyck K, Gambale JJ, Li S, Murphy GM, van Noort C, de Bruijn P, Verweij J. Aprepitant when added to a standard antiemetic regimen consisting of ondansetron and dexamethasone does not affect vinorelbine pharmacokinetics in cancer patients. Cancer Chemother Pharmacol. 2007 Feb;59(3):407-12. Epub 2006 Oct 19. PubMed PMID: 17051369.

85: Grote T, Hajdenberg J, Cartmell A, Ferguson S, Ginkel A, Charu V. Combination therapy for chemotherapy-induced nausea and vomiting in patients receiving moderately emetogenic chemotherapy: palonosetron, dexamethasone, and aprepitant. J Support Oncol. 2006 Sep;4(8):403-8. PubMed PMID: 17004515.

86: Warr D. The neurokinin1 receptor antagonist aprepitant as an antiemetic for moderately emetogenic chemotherapy. Expert Opin Pharmacother. 2006 Aug;7(12):1653-8. Review. PubMed PMID: 16872268.

87: Li SX, Pequignot E, Panebianco D, Lupinacci P, Majumdar A, Rosen L, Ahmed T, Royalty JE, Rushmore TH, Murphy MG, Petty KJ. Lack of effect of aprepitant on hydrodolasetron pharmacokinetics in CYP2D6 extensive and poor metabolizers. J Clin Pharmacol. 2006 Jul;46(7):792-801. PubMed PMID: 16809805.

88: Schmoll HJ, Aapro MS, Poli-Bigelli S, Kim HK, Park K, Jordan K, von Pawel J, Giezek H, Ahmed T, Chan CY. Comparison of an aprepitant regimen with a multiple-day ondansetron regimen, both with dexamethasone, for antiemetic efficacy in high-dose cisplatin treatment. Ann Oncol. 2006 Jun;17(6):1000-6. Epub 2006 Mar 8. PubMed PMID: 16524979.

89: Majumdar AK, Howard L, Goldberg MR, Hickey L, Constanzer M, Rothenberg PL, Crumley TM, Panebianco D, Bradstreet TE, Bergman AJ, Waldman SA, Greenberg HE, Butler K, Knops A, De Lepeleire I, Michiels N, Petty KJ. Pharmacokinetics of aprepitant after single and multiple oral doses in healthy volunteers. J Clin Pharmacol. 2006 Mar;46(3):291-300. PubMed PMID: 16490805.

90: Hesketh PJ, Grunberg SM, Herrstedt J, de Wit R, Gralla RJ, Carides AD, Taylor A, Evans JK, Horgan KJ. Combined data from two phase III trials of the NK1 antagonist aprepitant plus a 5HT 3 antagonist and a corticosteroid for prevention of chemotherapy-induced nausea and vomiting: effect of gender on treatment response. Support Care Cancer. 2006 Apr;14(4):354-60. Epub 2006 Feb 1. PubMed PMID: 16450086.

91: Keller M, Montgomery S, Ball W, Morrison M, Snavely D, Liu G, Hargreaves R, Hietala J, Lines C, Beebe K, Reines S. Lack of efficacy of the substance p (neurokinin1 receptor) antagonist aprepitant in the treatment of major depressive disorder. Biol Psychiatry. 2006 Feb 1;59(3):216-23. Epub 2005 Oct 24. PubMed PMID: 16248986.

92: Prommer E. Aprepitant (EMEND): the role of substance P in nausea and vomiting. J Pain Palliat Care Pharmacother. 2005;19(3):31-9. Review. PubMed PMID: 16219609.

93: Herrstedt J, Muss HB, Warr DG, Hesketh PJ, Eisenberg PD, Raftopoulos H, Grunberg SM, Gabriel M, Rodgers A, Hustad CM, Horgan KJ, Skobieranda F; Aprepitant Moderately Emetogenic Chemotherapy Study Group. Efficacy and tolerability of aprepitant for the prevention of chemotherapy-induced nausea and emesis over multiple cycles of moderately emetogenic chemotherapy. Cancer. 2005 Oct 1;104(7):1548-55. Erratum in: Cancer. 2006 Apr 1;106(7):1641. PubMed PMID: 16104039.

94: Depré M, Van Hecken A, Oeyen M, De Lepeleire I, Laethem T, Rothenberg P, Petty KJ, Majumdar A, Crumley T, Panebianco D, Bergman A, de Hoon JN. Effect of aprepitant on the pharmacokinetics and pharmacodynamics of warfarin. Eur J Clin Pharmacol. 2005 Jul;61(5-6):341-6. Epub 2005 Jun 28. PubMed PMID: 15983826.

95: Gralla RJ, de Wit R, Herrstedt J, Carides AD, Ianus J, Guoguang-Ma J, Evans JK, Horgan KJ. Antiemetic efficacy of the neurokinin-1 antagonist, aprepitant, plus a 5HT3 antagonist and a corticosteroid in patients receiving anthracyclines or cyclophosphamide in addition to high-dose cisplatin: analysis of combined data from two Phase III randomized clinical trials. Cancer. 2005 Aug 15;104(4):864-8. PubMed PMID: 15973669.

96: Warr DG, Grunberg SM, Gralla RJ, Hesketh PJ, Roila F, Wit R, Carides AD, Taylor A, Evans JK, Horgan KJ. The oral NK(1) antagonist aprepitant for the prevention of acute and delayed chemotherapy-induced nausea and vomiting: Pooled data from 2 randomised, double-blind, placebo controlled trials. Eur J Cancer. 2005 Jun;41(9):1278-85. PubMed PMID: 15939263.

97: Bergman AJ, Marbury T, Fosbinder T, Swan S, Hickey L, Bradstreet TE, Busillo J, Petty KJ, Aiyer KJ, Constanzer M, Huskey SE, Majumdar A. Effect of impaired renal function and haemodialysis on the pharmacokinetics of aprepitant. Clin Pharmacokinet. 2005;44(6):637-47. PubMed PMID: 15910011.

98: Shah AK, Hunt TL, Gallagher SC, Cullen MT Jr. Pharmacokinetics of palonosetron in combination with aprepitant in healthy volunteers. Curr Med Res Opin. 2005 Apr;21(4):595-601. PubMed PMID: 15899109.

99: Smith AR, Repka TL, Weigel BJ. Aprepitant for the control of chemotherapy induced nausea and vomiting in adolescents. Pediatr Blood Cancer. 2005 Nov;45(6):857-60. PubMed PMID: 15849684.

100: de Jonge ME, Huitema AD, Holtkamp MJ, van Dam SM, Beijnen JH, Rodenhuis S. Aprepitant inhibits cyclophosphamide bioactivation and thiotepa metabolism. Cancer Chemother Pharmacol. 2005 Oct;56(4):370-8. Epub 2005 Apr 19. PubMed PMID: 15838656.

101: Warr DG, Hesketh PJ, Gralla RJ, Muss HB, Herrstedt J, Eisenberg PD, Raftopoulos H, Grunberg SM, Gabriel M, Rodgers A, Bohidar N, Klinger G, Hustad CM, Horgan KJ, Skobieranda F. Efficacy and tolerability of aprepitant for the prevention of chemotherapy-induced nausea and vomiting in patients with breast cancer after moderately emetogenic chemotherapy. J Clin Oncol. 2005 Apr 20;23(12):2822-30. Erratum in: J Clin Oncol. 2005 Aug 20;23(24):5851. Dosage error in published abstract; MEDLINE/PubMed abstract corrected. PubMed PMID: 15837996.

102: Kline WF, Woolf EJ, Matuszewski BK. Assessment of the in-vivo stereochemical integrity of aprepitant based on the analysis of human plasma samples via high-performance liquid chromatography with mass spectrometric detection. Biomed Chromatogr. 2005 Sep;19(7):513-7. PubMed PMID: 15828059.

103: Viale PH. Integrating aprepitant and palonosetron into clinical practice: a role for the new antiemetics. Clin J Oncol Nurs. 2005 Feb;9(1):77-84. Review. PubMed PMID: 15751501.

104: Nygren P, Hande K, Petty KJ, Fedgchin M, van Dyck K, Majumdar A, Panebianco D, de Smet M, Ahmed T, Murphy MG, Gottesdiener KM, Cocquyt V, van Belle S. Lack of effect of aprepitant on the pharmacokinetics of docetaxel in cancer patients. Cancer Chemother Pharmacol. 2005 Jun;55(6):609-16. Epub 2005 Feb 19. PubMed PMID: 15723220.

105: Pendergrass K, Hargreaves R, Petty KJ, Carides AD, Evans JK, Horgan KJ. Aprepitant: an oral NK1 antagonist for the prevention of nausea and vomiting induced by highly emetogenic chemotherapy. Drugs Today (Barc). 2004 Oct;40(10):853-63. Review. PubMed PMID: 15605119.

106: Massaro AM, Lenz KL. Aprepitant: a novel antiemetic for chemotherapy-induced nausea and vomiting. Ann Pharmacother. 2005 Jan;39(1):77-85. Epub 2004 Nov 23. Review. PubMed PMID: 15562136.

107: Navari RM. Aprepitant: a neurokinin-1 receptor antagonist for the treatment of chemotherapy-induced nausea and vomiting. Expert Rev Anticancer Ther. 2004 Oct;4(5):715-24. Review. PubMed PMID: 15485308.

108: Chavez-Eng CM, Constanzer ML, Matuszewski BK. Simultaneous determination of Aprepitant and two metabolites in human plasma by high-performance liquid chromatography with tandem mass spectrometric detection. J Pharm Biomed Anal. 2004 Sep 3;35(5):1213-29. PubMed PMID: 15336366.

109: Stoutenburg JP, Raftopoulos H. Antiemetic studies on the NK1 receptor antagonist aprepitant. J Natl Compr Canc Netw. 2004 Sep;2(5):491-7. Review. PubMed PMID: 19780256.

110: Sanchez RI, Wang RW, Newton DJ, Bakhtiar R, Lu P, Chiu SH, Evans DC, Huskey SE. Cytochrome P450 3A4 is the major enzyme involved in the metabolism of the substance P receptor antagonist aprepitant. Drug Metab Dispos. 2004 Nov;32(11):1287-92. Epub 2004 Aug 10. PubMed PMID: 15304427.

111: Flemm LA. Aprepitant for chemotherapy-induced nausea and vomiting. Clin J Oncol Nurs. 2004 Jun;8(3):303-6. Review. PubMed PMID: 15208824.

112: Bergström M, Hargreaves RJ, Burns HD, Goldberg MR, Sciberras D, Reines SA, Petty KJ, Ogren M, Antoni G, Långström B, Eskola O, Scheinin M, Solin O, Majumdar AK, Constanzer ML, Battisti WP, Bradstreet TE, Gargano C, Hietala J. Human positron emission tomography studies of brain neurokinin 1 receptor occupancy by aprepitant. Biol Psychiatry. 2004 May 15;55(10):1007-12. PubMed PMID: 15121485.

113: Moreno Alvarez PJ. [Aprepitant (Emend). Laboratory: Merck & Co., Inc]. Farm Hosp. 2004 Mar-Apr;28(2):145-6. Spanish. PubMed PMID: 15101808.

114: Olver IN. Aprepitant in antiemetic combinations to prevent chemotherapy-induced nausea and vomiting. Int J Clin Pract. 2004 Feb;58(2):201-6. Review. PubMed PMID: 15055869.

115: Dando TM, Perry CM. Aprepitant: a review of its use in the prevention of chemotherapy-induced nausea and vomiting. Drugs. 2004;64(7):777-94. Review. PubMed PMID: 15025555.

116: Shadle CR, Lee Y, Majumdar AK, Petty KJ, Gargano C, Bradstreet TE, Evans JK, Blum RA. Evaluation of potential inductive effects of aprepitant on cytochrome P450 3A4 and 2C9 activity. J Clin Pharmacol. 2004 Mar;44(3):215-23. PubMed PMID: 14973304.

117: de Wit R, Herrstedt J, Rapoport B, Carides AD, Guoguang-Ma J, Elmer M, Schmidt C, Evans JK, Horgan KJ. The oral NK(1) antagonist, aprepitant, given with standard antiemetics provides protection against nausea and vomiting over multiple cycles of cisplatin-based chemotherapy: a combined analysis of two randomised, placebo-controlled phase III clinical trials. Eur J Cancer. 2004 Feb;40(3):403-10. PubMed PMID: 14746859.

118: Huskey SE, Dean BJ, Doss GA, Wang Z, Hop CE, Anari R, Finke PE, Robichaud AJ, Zhang M, Wang B, Strauss JR, Cunningham PK, Feeney WP, Franklin RB, Baillie TA, Chiu SH. The metabolic disposition of aprepitant, a substance P receptor antagonist, in rats and dogs. Drug Metab Dispos. 2004 Feb;32(2):246-58. PubMed PMID: 14744948.

119: Patel L, Lindley C. Aprepitant--a novel NK1-receptor antagonist. Expert Opin Pharmacother. 2003 Dec;4(12):2279-96. Review. PubMed PMID: 14640927.

120: de Wit R, Herrstedt J, Rapoport B, Carides AD, Carides G, Elmer M, Schmidt C, Evans JK, Horgan KJ. Addition of the oral NK1 antagonist aprepitant to standard antiemetics provides protection against nausea and vomiting during multiple cycles of cisplatin-based chemotherapy. J Clin Oncol. 2003 Nov 15;21(22):4105-11. Epub 2003 Oct 14. PubMed PMID: 14559891.

121: Hesketh PJ, Grunberg SM, Gralla RJ, Warr DG, Roila F, de Wit R, Chawla SP, Carides AD, Ianus J, Elmer ME, Evans JK, Beck K, Reines S, Horgan KJ; Aprepitant Protocol 052 Study Group. The oral neurokinin-1 antagonist aprepitant for the prevention of chemotherapy-induced nausea and vomiting: a multinational, randomized, double-blind, placebo-controlled trial in patients receiving high-dose cisplatin--the Aprepitant Protocol 052 Study Group. J Clin Oncol. 2003 Nov 15;21(22):4112-9. Epub 2003 Oct 14. PubMed PMID: 14559886.

122: Feuring M, Lee Y, Orlowski LH, Michiels N, De Smet M, Majumdar AK, Petty KJ, Goldberg MR, Murphy MG, Gottesdiener KM, Hesney M, Brackett LE, Wehling M. Lack of effect of aprepitant on digoxin pharmacokinetics in healthy subjects. J Clin Pharmacol. 2003 Aug;43(8):912-7. PubMed PMID: 12953348.

123: Majumdar AK, McCrea JB, Panebianco DL, Hesney M, Dru J, Constanzer M, Goldberg MR, Murphy G, Gottesdiener KM, Lines CR, Petty KJ, Blum RA. Effects of aprepitant on cytochrome P450 3A4 activity using midazolam as a probe. Clin Pharmacol Ther. 2003 Aug;74(2):150-6. PubMed PMID: 12891225.

124: Aprepitant (emend) for prevention of nausea and vomiting due to cancer chemotherapy. Med Lett Drugs Ther. 2003 Aug 4;45(1162):62-3. PubMed PMID: 12888739.

125: Blum RA, Majumdar A, McCrea J, Busillo J, Orlowski LH, Panebianco D, Hesney M, Petty KJ, Goldberg MR, Murphy MG, Gottesdiener KM, Hustad CM, Lates C, Kraft WK, Van Buren S, Waldman SA, Greenberg HE. Effects of aprepitant on the pharmacokinetics of ondansetron and granisetron in healthy subjects. Clin Ther. 2003 May;25(5):1407-19. Review. PubMed PMID: 12867217.

126: McCrea JB, Majumdar AK, Goldberg MR, Iwamoto M, Gargano C, Panebianco DL, Hesney M, Lines CR, Petty KJ, Deutsch PJ, Murphy MG, Gottesdiener KM, Goldwater DR, Blum RA. Effects of the neurokinin1 receptor antagonist aprepitant on the pharmacokinetics of dexamethasone and methylprednisolone. Clin Pharmacol Ther. 2003 Jul;74(1):17-24. PubMed PMID: 12844131.

127: Martin AR, Carides AD, Pearson JD, Horgan K, Elmer M, Schmidt C, Cai B, Chawla SP, Grunberg SM. Functional relevance of antiemetic control. Experience using the FLIE questionnaire in a randomised study of the NK-1 antagonist aprepitant. Eur J Cancer. 2003 Jul;39(10):1395-401. PubMed PMID: 12826042.

128: Poli-Bigelli S, Rodrigues-Pereira J, Carides AD, Julie Ma G, Eldridge K, Hipple A, Evans JK, Horgan KJ, Lawson F; Aprepitant Protocol 054 Study Group. Addition of the neurokinin 1 receptor antagonist aprepitant to standard antiemetic therapy improves control of chemotherapy-induced nausea and vomiting. Results from a randomized, double-blind, placebo-controlled trial in Latin America. Cancer. 2003 Jun 15;97(12):3090-8. PubMed PMID: 12784346.

129: Huskey SE, Dean BJ, Bakhtiar R, Sanchez RI, Tattersall FD, Rycroft W, Hargreaves R, Watt AP, Chicchi GG, Keohane C, Hora DF, Chiu SH. Brain penetration of aprepitant, a substance P receptor antagonist, in ferrets. Drug Metab Dispos. 2003 Jun;31(6):785-91. PubMed PMID: 12756213.

130: Chawla SP, Grunberg SM, Gralla RJ, Hesketh PJ, Rittenberg C, Elmer ME, Schmidt C, Taylor A, Carides AD, Evans JK, Horgan KJ. Establishing the dose of the oral NK1 antagonist aprepitant for the prevention of chemotherapy-induced nausea and vomiting. Cancer. 2003 May 1;97(9):2290-300. PubMed PMID: 12712486.

131: Brands KM, Payack JF, Rosen JD, Nelson TD, Candelario A, Huffman MA, Zhao MM, Li J, Craig B, Song ZJ, Tschaen DM, Hansen K, Devine PN, Pye PJ, Rossen K, Dormer PG, Reamer RA, Welch CJ, Mathre DJ, Tsou NN, McNamara JM, Reider PJ. Efficient synthesis of NK(1) receptor antagonist aprepitant using a crystallization-induced diastereoselective transformation. J Am Chem Soc. 2003 Feb 26;125(8):2129-35. PubMed PMID: 12590540.

132: Helmy R, Zhou GX, Chen YW, Crocker L, Wang T, Wenslow RM Jr, Vailaya A. Characterization and quantitation of aprepitant drug substance polymorphs by attenuated total reflectance fourier transform infrared spectroscopy. Anal Chem. 2003 Feb 1;75(3):605-11. PubMed PMID: 12585491.

133: Zhao MM, McNamara JM, Ho GJ, Emerson KM, Song ZJ, Tschaen DM, Brands KM, Dolling UH, Grabowski EJ, Reider PJ, Cottrell IF, Ashwood MS, Bishop BC. Practical asymmetric synthesis of aprepitant, a potent human NK-1 receptor antagonist, via a stereoselective Lewis acid-catalyzed trans acetalization reaction. J Org Chem. 2002 Sep 20;67(19):6743-7. PubMed PMID: 12227806.

134: MK 869. Aprepitant, L 754030, MK 0869. Drugs R D. 2002;3(3):200-3. Review. PubMed PMID: 12099168.