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The correlation between plasma aprepitant concentration and antiemetic effect in Japanese gastric or esophageal cancer patients

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Abstract

Background

Chemotherapy-induced nausea and vomiting (CINV) are significant problems in cancer patients, but a correlation between plasma aprepitant concentration and antiemetic effect has not been reported. This study aimed to characterize the correlation between plasma aprepitant concentration and clinical antiemetic effect in a limited group of Japanese gastric or esophageal cancer patients.

Methods

Thirty-three Japanese cancer patients receiving cisplatin-based chemotherapy for the first time following oral aprepitant (125 mg on day 1 and 80 mg on days 2 and 3) were enrolled. The plasma aprepitant concentrations 48 h after the first administration were determined using liquid chromatography–mass spectrometry. Patients were allocated to the high-concentration group (plasma aprepitant concentration was >331.1 ng/ml) or the low-concentration group (plasma aprepitant concentration was ≤331.1 ng/ml) to investigate the relationship between plasma aprepitant concentration and antiemetic effects.

Results

No significant differences were found between the two groups in terms of percentage of CINV prevention. Of 13 patients who experienced CINV [MASCC Antiemesis Tool (MAT) score >3], those in the high-concentration group showed a significant improvement in CINV following aprepitant administration (days 1–3).

Conclusion

The present study suggests that the antiemetic effect of aprepitant is associated with plasma aprepitant concentration. A plasma aprepitant concentration of 331.1 ng/ml may be a valid threshold for identifying its optimal antiemetic effects in Japanese gastric or esophageal cancer patients.

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References

  1. Bergström M, Hargreaves RJ, Burns HD et al (2004) Human positron emission tomography studies of brain neurokinin 1 receptor occupancy by aprepitant. Biol Psychiatry 55:1007–1012

    Article  PubMed  Google Scholar 

  2. (2014) Interview form of Emend® capsules 125 mg, revised 7th edn. Ono Pharmaceutical Co., Ltd, Osaka

  3. Takahashi T, Nakamura Y, Tsuya A et al (2011) 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 68:653–659

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  4. Motohashi S, Mino Y, Hori K et al (2013) Interindividual variations in aprepitant plasma pharmacokinetics in cancer patients receiving cisplatin-based chemotherapy for the first time. Biol Pharm Bull 36:676–681

    Article  CAS  PubMed  Google Scholar 

  5. Nakade S, Ohno T, Kitagawa J et al (2008) Population pharmacokinetics of aprepitant and dexamethasone in the prevention of chemotherapy-induced nausea and vomiting. Cancer Chemother Pharmacol 63:75–83

    Article  CAS  PubMed  Google Scholar 

  6. Ando N, Kato H, Igaki H et al (2012) A randomized trial comparing postoperative adjuvant chemotherapy with cisplatin and 5-fluorouracil versus preoperative chemotherapy for localized advanced squamous cell carcinoma of the thoracic esophagus (JCOG9907). Ann Surg Oncol 19:68–74

    Article  PubMed  Google Scholar 

  7. Kato H, Sato A, Fukuda H et al (2009) A phase II trial of chemoradiotherapy for stage I esophageal squamous cell carcinoma: Japan Clinical Oncology Group Study (JCOG9708). Jpn J Clin Oncol 39:638–643

    Article  PubMed  Google Scholar 

  8. Koizumi W, Narahara H, Hara T et al (2008) S-1 plus cisplatin versus S-1 alone for first-line treatment of advanced gastric cancer (SPIRITS trial): a phase III trial. Lancet Oncol 9:215–221

    Article  CAS  PubMed  Google Scholar 

  9. Molassiotis A, Coventry PA, Stricker CT et al (2007) Validation and psychometric properties of a short clinical scale to measure chemotherapy-induced nausea and vomiting: the MASCC Antiemesis Tool. J Pain Symptom Manag 34:148–159

    Article  Google Scholar 

  10. Sanchez RI, Wang RW, Newton DJ et al (2004) Cytochrome P450 3A4 is the major enzyme involved in the metabolism of the substance P receptor antagonist aprepitant. Drug Metab Dispos 32:1287–1292

    Article  CAS  PubMed  Google Scholar 

  11. Rolia F, Tonato M, Basurto C et al (1989) Protection from nausea and vomiting in cisplatin-treated patients: high-dose metoclopramide combined with methylprednisolone vs. metoclopramide combined with dexamethasone and diphenhydramine: a study of the Italian Oncology Group for Clinical Research. J Clin Oncol 7:1693–1700

    Google Scholar 

  12. Majumdar AK, Howard L, Goldberg MR et al (2006) Pharmacokinetics of aprepitant after single and multiple oral doses in healthy volunteers. J Clin Pharmacol 46:291–300

    Article  CAS  PubMed  Google Scholar 

Download references

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Pharmacy, Toho University Omori Medical Center, 6-11-1, Omori-nishi, Ota-ku, Tokyo, 143-8541, Japan

    Kosuke Nishizawa & Kenji Nishizawa

  2. Department of Surgery, School of Medicine, Toho University, 6-11-1, Omori-nishi, Ota-ku, Tokyo, 143-8541, Japan

    Hideaki Shimada, Masaaki Ito, Yoko Oshima, Satoshi Yajima & Hironori Kaneko

  3. Division of Gastroenterology and Hepatology, Department of Internal Medicine (Omori), School of Medicine, Faculty of Medicine, Toho University, 5-21-16, Omori-nishi, Ota-ku, Tokyo, 143-8540, Japan

    Yoshinori Kikuchi & Yasukiyo Sumino

  4. Department of Clinical Pharmaceutics, School of Pharmaceutical Sciences, Toho University, 2-2-1, Miyama, Funabashi, Chiba, 274-8510, Japan

    Masahiko Obayashi

Authors
  1. Kosuke Nishizawa
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  2. Hideaki Shimada
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  3. Masaaki Ito
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  4. Yoko Oshima
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  5. Satoshi Yajima
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  6. Yoshinori Kikuchi
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  7. Yasukiyo Sumino
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  8. Hironori Kaneko
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  9. Kenji Nishizawa
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  10. Masahiko Obayashi
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Corresponding author

Correspondence to Kosuke Nishizawa.

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Nishizawa, K., Shimada, H., Ito, M. et al. The correlation between plasma aprepitant concentration and antiemetic effect in Japanese gastric or esophageal cancer patients. Int J Clin Oncol 20, 538–542 (2015). https://doi.org/10.1007/s10147-014-0747-6

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  • DOI: https://doi.org/10.1007/s10147-014-0747-6

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