Association of pharmacokinetics or pharmacogenomics with toxicity of erlotinib in patients with advanced non-small cell lung cancer

晚期非小细胞肺癌患者的药代动力学或药物基因组学与厄洛替尼毒性的关联

• 批准号: 23590648
• 负责人: HIROSE Takashi
• 金额: $ 2.66万
• 依托单位: Tokyo National Hospital (Clinical research) (2013)Showa University (2011-2012)
• 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-23590648/
• 关键词: ファーマコゲノミクス

The orally administered erlotinib showed large interindividual variability in its pharmacokinetics. The aim of this study was to evaluate the association of pharmacokinetics or pharmacogenomics with toxicity of erlotinib in patients with advanced NSCLC. Plasma concentration of erlotinib was analyzed by high-performance liquid chromatography. The genotypes of ABCG2, ABCB1, ABCC2, CYP3A4, CYP3A5, CYP1A1, and CYP1A2 were analyzed by direct sequencing.There were no statistically significant association of pharmacokinetics or pharmacogenomics with toxicity, such as skin toxicity, diarrhea, stomatitis, liver injury, and interstitial lung disease (ILD) of erlotinib. However, one patient died of drug induced ILD was homozygous for ABCG2 C>A and showed the highest AUC. Additionally, Cmax was trend toward to higher in 4 patients with liver injury than those without (p=0.054). In conclusion, the homozygote of ABCG2 C>A could be associated with elevated erlotinib exposure and drug-induced ILD.

口服厄洛替尼的药代动力学表现出较大的个体间差异。本研究的目的是评价厄洛替尼在晚期NSCLC患者中的药代动力学或药物基因组学与毒性的相关性。通过高效液相色谱法分析厄洛替尼的血浆浓度。直接测序分析ABCG 2、ABCB 1、ABCC 2、CYP3A4、CYP3A5、CYP1A1和CYP1A2基因型，厄洛替尼的皮肤毒性、腹泻、口腔炎、肝损伤和间质性肺疾病（ILD）等毒性与药代动力学或药物基因组学无统计学显著相关性。然而，1例患者死于药物诱导的ILD，其为ABCG 2 C>A纯合子，并显示出最高的AUC。此外，4例肝损伤患者的Cmax有高于无肝损伤患者的趋势（p=0.054）。总之，ABCG 2 C>A纯合子可能与厄洛替尼暴露量升高和药物诱导的ILD相关。

项目成果

ssociation of pharmacokinetics or pharmacogenomics with toxicity of erlotinib in patients with advanced NSCLC

晚期 NSCLC 患者的药代动力学或药物基因组学与厄洛替尼毒性的关联

• 作者: Takashi Hirose;Ken-ichi Fujita;Sojiro Kusumoto;Takao Shirai;Tomohide Sugiyama;Masanao Nakashima;Tohru Ohmori;Yasutsuna Sasaki;Atsuhisa Tamura ;Ken Ohta
• 通讯作者: Ken Ohta

非小細胞肺癌に対するエルロチニブの毒性に影響を与える薬物動態、薬理遺伝学的検討

影响厄洛替尼治疗非小细胞肺癌毒性的药代动力学和药物遗传学研究

• 发表时间: 2014
• 作者: 長谷川寛雄;塚崎邦弘;宮崎康司;上平憲;廣瀬 敬
• 通讯作者: 廣瀬 敬

Association of pharmacokinetics or pharmacogenomics with toxicity of erlotinib in patients with advanced NSCLC

晚期 NSCLC 患者的药代动力学或药物基因组学与厄洛替尼毒性的关联

• 发表时间: 2014
• 作者: 長谷川寛雄;鶴田一人;佐々木大介;森沙耶香;土井裕子;石原香織;長井一浩;栁原克紀;塚崎邦弘;宮崎康司;上平憲;廣瀬 敬
• 通讯作者: 廣瀬 敬