Department of Pharmacology & Toxicology, School of Biomedical Sciences, University of Otago, Dunedin, New Zealand.
Department of Pharmacology & Toxicology, School of Biomedical Sciences, University of Otago, Dunedin, New Zealand,
Pharmacology. 2020;105(11-12):715-718. doi: 10.1159/000506996. Epub 2020 May 27.
Crizotinib is a tyrosine kinase inhibitor used to treat anaplastic lymphoma kinase-positive lung cancer. There is in vitro evidence that crizotinib may auto-inhibit cytochrome P450 3A (CYP3A) activity, with important implications for crizotinib pharmacokinetics. In order to test whether crizotinib treatment alters CYP3A activity in vivo, mice were treated with 5 and 25 mg/kg crizotinib (p.o.) daily for 14 days. Results showed that crizotinib treatment did not alter CYP3A activity as determined by erythromycin N-demethylation. In addition, CYP3A polypeptide expression as measured by Western blot was unchanged. Therefore, our results do not support CYP3A inhibition by crizotinib in vivo.
克唑替尼是一种用于治疗间变性淋巴瘤激酶阳性肺癌的酪氨酸激酶抑制剂。有体外证据表明，克唑替尼可能会自动抑制细胞色素 P450 3A（CYP3A）的活性，这对克唑替尼的药代动力学有重要影响。为了测试克唑替尼治疗是否会改变体内 CYP3A 的活性，用 5 和 25mg/kg 克唑替尼（口服）每天处理小鼠 14 天。结果表明，克唑替尼治疗并没有改变红霉素 N-去甲基化所测定的 CYP3A 活性。此外，用 Western blot 测定的 CYP3A 多肽表达也没有变化。因此，我们的结果不支持克唑替尼在体内抑制 CYP3A。
