中国临床药理学与治疗学2018，Vol.23Issue(10)：1147-1152,6.DOI:10.12092/j.issn.1009-2501.2018.10.010
艾维替尼在一组中国晚期非小细胞肺癌病人体内单多次给药代谢产物的药代动力学研究
Pharmacokinetics of the metabolites of abivertinib in Chinese patients with advanced NSCLC in a single and multiple dose group
摘要
Abstract
AIM: To evaluate the pharmacoki-netics of the metabolites of abivertinib in Chinese patients with advanced nonsmall-cell lung cancer ( NSCLC) after single and multiple dose of abiver-tinib maleate capsules. METHODS: Seven Chinese patients with advanced NSCLC were administered a single oral dose of 350 mg of abivertinib maleate capsule. After a washout period, three of them were administered 350 mg of abivertinib QD for 28 days, four were administered 175 mg of abivertinib twice a day for 28 days. The plasma concentrations of five metabolites of abivertinib were assayed with liquid chromatography-tandem mass spectrometry ( LC-MS/MS) . Pharmacokinetic parameters were calculated with WinNonlin ver. 6. 4. RESULTS:Among these five metabolites, the exposure of MII-2, a cysteine conjugate, was the highest, which was 3. 32%-5. 57% of the exposure of the parent drug. The ex-posures of M1 ( N-demethylation) and M2 ( N-oxi-dation) were 2. 14%-4. 24% and 0. 56%-1. 00% of the exposure of the parent drug, respectively. The exposures of M4 ( N-dealkylation) and MII-1 ( ace-tylcysteine conjugate) were low, most of the concen-trations of MII-1 were blow the lower limit of quanti-tation (0.1 ng/mL). CONCLUSION:The expo-sures of the five metabolites monitored were no more than 10% of the exposure of the parent drug.关键词
艾维替尼/代谢产物/药代动力学/表皮生长因子受体酪氨酸激酶抑制剂/液相-质谱联用Key words
abivertinib/metabolite/pharmaco-kinetics/EGFR-TKI/liquid chromatography-tandem mass spectrometry分类
医药卫生引用本文复制引用
王璐,郑昕,王维聪,赵洪云,马宇翔,张力,胡蓓,江骥..艾维替尼在一组中国晚期非小细胞肺癌病人体内单多次给药代谢产物的药代动力学研究[J].中国临床药理学与治疗学,2018,23(10):1147-1152,6.基金项目
国家自然科学基金青年基金(81503164) （81503164）
十二五重大新药创制重大专项(2013ZX09401003) （2013ZX09401003）
