的药动学特征Gilteritinib: flt3酪氨酸激酶抑制剂。

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詹姆斯AJ,史密斯CC, Litzow M, Perl AE,奥特曼JK,谢泼德D, Kadokura T,绍达K,巴顿M,陆Z,刘C, Moy年代,李维斯MJ, Bahceci E

的药动学特征Gilteritinib: flt3酪氨酸激酶抑制剂。

Pharmacokinet。2020年10月,59 (10):1273 - 1290。doi: 10.1007 / s40262 - 020 - 00888 - w。

PubMed ID

32304015 (在PubMed

]

文摘

背景和目的:Gilteritinib是一种新型的、高选择性的酪氨酸激酶抑制剂批准在美国,加拿大,欧洲,巴西,韩国,和日本治疗FLT3 mutation-positive急性髓系白血病(aml)。本文描述了临床gilteritinib的药动学特征。方法:gilteritinib的药动学特征是评估从五个临床研究。结果:Dose-proportional药物动力学观察后每日一次gilteritinib政府(20 - 450毫克剂量范围)。最大浓度中位数2 - 6 h后达成单一和重复剂量gilteritinib;意味着消除半衰期是113 h。消除主要是通过粪便。接触gilteritinib禁食和美联储条件下相当。Gilteritinib主要是通过细胞色素P450 (CYP) 3 a4代谢;共同的gilteritinib伊曲康唑(22抑制剂和CYP3A4抑制剂)或利福平(22强诱导物和CYP3A诱导物)显著影响gilteritinib药代动力学资料。没有观察到当gilteritinib coadministered临床相关的交互与咪达唑仑(CYP3A4衬底)或头孢氨苄(多种药物和毒素挤压1衬底)。 Unbound gilteritinib exposure was similar between subjects with hepatic impairment and normal hepatic function. CONCLUSIONS: Gilteritinib exhibits a dose-proportional pharmacokinetic profile in healthy subjects and in patients with relapsed/refractory acute myeloid leukemia. Gilteritinib exposure is not significantly affected by food. Moderate-to-strong CYP3A inhibitors demonstrated a significant effect on gilteritinib exposure. Coadministration of gilteritinib with CYP3A4 or multidrug and toxin extrusion 1 substrates did not impact substrate concentrations. Unbound gilteritinib was comparable between subjects with hepatic impairment and normal hepatic function; dose adjustment is not warranted for patients with hepatic impairment. CLINICAL TRIAL REGISTRATION: NCT02014558, NCT02456883, NCT02571816.

DrugBank数据引用了这篇文章

药物酶

药物	酶	类	生物	药理作用	行动
Gilteritinib	细胞色素P450 3 a4	蛋白质	人类	没有	底物	细节