Investigation of relationship between the pharmacokinetics of and clinical responses to prochlorperazine in patients receiving opioids

• Project/Area Number: 23790181
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Medical pharmacy
• Research Institution: Hamamatsu University School of Medicine
• Principal Investigator: NAITO Takafumi 浜松医科大学, 医学部附属病院, 副薬剤部長 (80422749)
• Research Collaborator: TASHIRO Masaki 浜松医科大学, 医学部附属病院, 薬剤師
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2012: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2011: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: プロクロルペラジン / オピオイド / 薬物動態 / 有害作用 / ドパミンD2受容体 / オピオイドμ1受容体 / 遺伝子多型 / 緩和医療 / オキシコドン / オピオイド誘発性嘔吐 / プロラクチン / がん性疼痛 / 制吐薬 / 代謝物 / TDM

Research Abstract

Prochlorperazine has a high potency antiemetic effect based on inhibiting dopamine D2 receptor and is commonly used for the treatment of opioid-induced nausea and vomiting in cancer patients. Clinical responses to prochlorperazine vary in patients receiving opioids. Opioids bind to opioid receptor mu1 on the hypothalamus and subsequently cause the blockade of dopaminergic pathways. This study evaluated the interindividual variation in pharmacokinetics of and clinical responses to prochlorperazine based on non-genetic and genetic factors in patients receiving opioids.

Research Products

• [Journal Article] Impact of genetic and non-genetic factors on clinical responses to prochlorperazine in oxycodone-treated cancer patients. (2014)
  • Author(s): Tashiro M, Naito T, Ohnishi K, Kagawa Y, Kawakami J.
  • Journal Title: Clin Chim Acta. Volume: 429 Pages: 175-180
  • DOI: 10.1016/j.cca.2013.12.011
  • Peer Reviewed
• [Journal Article] Simultaneous determination of prochlorperazine and its metabolites in human plasma using isocratic liquid chromatography tandem mass spectrometry (2012)
  • Author(s): Tashiro M, Naito T, Kagawa Y, Kawakami J
  • Journal Title: Biomed Chromatogr Volume: 26 Issue: 6 Pages: 754-760
  • DOI: 10.1002/bmc.1725
• [Presentation] Relationships between prochlorperazine pharmacokinetics and Its clinical responses based on DRD2 gene polymorphisms in cancer patients receiving opioid analgesics (2011)
  • Author(s): Tashiro M, Naito T, Takashina Y, Kagawa Y, Kawakami J
  • Organizer: 10th Congress of the European Association for Clinical Pharmacology and Therapeutics
  • Place of Presentation: Budapest, Hungary
• [Presentation] がん患者におけるプロクロルペラジンの制吐作用および有害作用に及ぼすDRD2の遺伝子変異の影響 (2011)
  • Author(s): 田代将貴,内藤隆文,賀川義之,川上純一
  • Organizer: 第21回日本医療薬学会年会
  • Place of Presentation: 神戸