Therapeutic drug management of tyrosine kinase inhibitor

酪氨酸激酶抑制剂的治疗药物管理

• 批准号: 23590168
• 负责人: MIURA MASATOMO
• 金额: $ 3.33万
• 依托单位: Akita University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2013
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23590168/
• 关键词: 分子標的抗がん剤; TDM; 遺伝子多型; 分子標的治療薬; 血中濃度; 個別化療法

Because of the variability in tyrosine kinase inhibitor(TKI) exposure among patients, therapeutic drug monitoring (TDM) to maintain a certain fixed plasma threshold level would be beneficial during TKI therapy. TDM service should be routinely provided to patients taking TKI. Patients at increased hyperbilirubinemia risk could be identified by prospective UGT1A1 genotyping prior to nilotinib therapy. The efficacy of the threshold plasma trough concentration of nilotinib should be set above 800 ng/mL for CML patients. Dasatinib efficacy and safety were associared with exposure (AUC). A lower dasatinib exposure was detected among patients with T315I compared to those without the mutation. These data suggest that sufficient exposure of dasatinib may prohibit clonal evolution by adequately inhibiting BCR-ABL kinase. And plasma trough concentration of dasatinib should not exceed 2.5 ng/mL in CML patients.

由于患者在酪氨酸激酶抑制剂（TKI）暴露方面的差异，在TKI治疗期间，维持一定的固定血浆阈值水平的治疗性药物监测（TDM）将是有益的。对TKI患者应常规提供TDM服务。在尼罗替尼治疗前，可以通过前瞻性UGT1A1基因分型来确定高胆红素血症风险增加的患者。尼罗替尼对CML患者的疗效阈值血浆谷浓度应设定在800 ng/mL以上。达沙替尼的疗效和安全性与暴露量（AUC）相关。与没有突变的患者相比，T315I患者的达沙替尼暴露量较低。这些数据表明，充分暴露于达沙替尼可能通过充分抑制BCR-ABL激酶来阻止克隆进化。CML患者达沙替尼血药谷浓度不应超过2.5 ng/mL。

项目成果

Bile acid is important for gastrointestinal absorption of nilotinib.

胆汁酸对于尼洛替尼的胃肠道吸收很重要。

• DOI: 10.1007/s00228-012-1282-x
• 发表时间: 2012
• 期刊: Eur J Clin Pharmacol.
• 作者: Fujimi A;Takahashi N;Miura M;Kanisawa Y;Ono K;Sawada K.
• 通讯作者: Sawada K.

Multicenter phase II clinical trial of nilotinib for patients with imatinib-resistant or -intolerant chronic myeloid leukemia from the East Japan CML study group evaluation of molecular response and the efficacy and safety of nilotinib.

• DOI: 10.1186/2050-7771-2-6
• 发表时间: 2014-03-20
• 期刊: Biomarker research
• 影响因子: 11.1
• 作者: Takahashi N;Miura M;Kuroki J;Mitani K;Kitabayashi A;Sasaki O;Kimura H;Imai K;Tsukamoto N;Noji H;Kondo T;Motegi M;Kato Y;Mita M;Saito H;Yoshida C;Torimoto Y;Kimura T;Wano Y;Nomura J;Yamamoto S;Mayama K;Honma R;Sugawara T;Sato S;Shinagawa A;Abumiya M;Niioka T;Harigae H;Sawada K
• 通讯作者: Sawada K

遺伝子多型情報とTDMに基づいたイマチニブ個別化療法

基于基因多态性信息和TDM的伊马替尼个体化治疗

• 发表时间: 2011
• 作者: Iwamura;A.;Fukami;T.;Higuchi;R.;Nakajima;M.;and Yokoi;T;三浦昌朋
• 通讯作者: 三浦昌朋

進行性腎細胞がん患者におけるスニチニブ血中濃度モニタリングによる副作用発現予測の検討

通过监测晚期肾细胞癌患者舒尼替尼血药浓度预测副作用的检验

• 发表时间: 2013
• 作者: Abumiya M;Miura M;Takahashi N;Niioka T;Sawada K;安達啓一;豊平由美子・小原剛・稲垣博英・坂巻路可・高橋浩二郎・柳原延章;藤山信弘，土谷順彦，羽渕友則，三浦昌朋
• 通讯作者: 藤山信弘，土谷順彦，羽渕友則，三浦昌朋

Inter- and intra-individual variability of nilotinib plasma trough concentration in CML patients.

CML 患者尼洛替尼血浆谷浓度的个体间和个体内变异性。

• 发表时间: 2013
• 作者: 2)Maiko Abumiya;Masatomo Miura;Naoto Takahashi;Takenori Niioka;Kenichi Sawada
• 通讯作者: Kenichi Sawada