演題詳細

一般口演 / Oral Session

一般口演 25 (Oral Session 25) :CML:基礎 2

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日程
2013年10月11日(金)
時間
14:25 - 15:25
会場
第7会場 / Room No.7 (ロイトン札幌 2F リージェント)
座長・司会
中前 博久 (Hirohisa Nakamae):1
1:大阪市立大学大学院医学研究科 血液腫瘍制御学
 
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Pharmacokinetic (PK) and Pharmacodynamic (PD) Study of Dasatinib in CML-CP

演題番号 : OS-1-129

石田 陽治 (Yoji Ishida):1,3、村井 一範 (Kazunori Murai):1,3、山口 公平 (Kohei Yamaguchi):3、宮城島 拓人 (Takuto Miyagishima):3、進藤 基博 (Motohiro Shindo):3、小川 一英 (Kazuei Ogawa):3、永嶋 貴博 (Takahiro Nagashima):3、佐藤 伸二 (Shinji Sato):3、渡部 玲子 (Reiko Watanabe):3、山本 聡 (Satoshi Yamamoto):3、廣瀬 貴之 (Takayuki Hirose):3、齊藤 宗一 (Sohichi Saitoh):3、米積 昌克 (Masakatsu Yonezumi):3、近藤 健 (Takeshi Kondo):3、加藤 裕一 (Yuichi Kato):3、望月 伸夫 (Nobuo Mochizuki):2、大野 恵子 (Keiko Ohno):2、岸野 官吏 (Satoshi Kishino):2、伊藤 薫樹 (Shigeki Ito):1,3、久保 恒明 (Koumei Kubo):3

1:Hematology/ Oncology, Iwate Medical University School of Medicine、2:Meiji Pharmaceutical University、3:Inter-Michinoku Dasatinib Study Group

 

Purpose: Dasatinib is a novel kinase inhibitor of BCR-ABL and SRC family kinases. Dasatinib has shown promising anti-leukemic activity in CML. We performed the PK and PD analysis of dasatinib in newly diagnosed CML patients.Methods: The PK analysis of dasatinib: The plasma concentrations of dasatinib (1, 2, 4 hr after taking dasatinib post 28days) were determined by HPLC with mass spectrometry. PD analysis of dasatinib: Phospho-CrkL in CD 34 positive cells was analyzed by flow cytometry after incubation of bone marrow mononuclear cells with dasatinib for 2 hours. Inhibitory concentration at 50% (IC50) was determined by dose-responsive curve. The efficacy: The efficacy was defined as expression of bcr/able at 1 month, measured by the RQ-PCR with international scale, or the reduction rate(%), bcr/abl expression at 1 month divided by that at diagnosis. PK/PD analysis: Area under the curve (AUC) and time above IC50 were calculated using Phonix WinNonlin 6.3. Results: Twenty-eight newly diagnosed CML-CP patients were included. The efficacy(expression of bcr/abl at 1 month) was not correlated with AUC, Cmax, AUC/IC50 and Cmax/IC50 but significantly correlated with TAIC50 (r=0.476, p=0.01). The reduction rate was correlated significantly with only TAIC50(r=0.514, p=0.005). Eight cases(53.3%) reached MMR at 3 month among 15, whose TAIC50s were more than 12 hrs, while only 2 cases(15.4%) reached MMR among 13 with less than 12 hrs. Conclusion: Dasatinib has anti-leukemic activity in a time dependent manner. Exposure more than 12 hrs at TAIC50 will get benefits of better prognosis.

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