摘要
目的 :建立稳定高效的原代大鼠肝细胞和冻存人肝细胞诱导实验模型,研究SPH0396对CYP1A2和CYP3A4的诱导。方法 :利用探针底物代谢物生成量对CYP3A4和CYP1A2的酶活性进行评价。结果 :SPH0396在0.1mmol/L和1 mmol/L对CYP酶(1A2和3A4)无诱导作用,3 mmol/L时对CYP 3A4无诱导,而对CYP1A2的诱导倍数均大于2,初步认为其诱导CYP1A2,且诱导作用在原代大鼠与冻存人肝细胞中无种属差异。结论 :SPH0396能诱导CYP1A2,需关注SPH0396因诱导CYP1A2而导致临床上发生药物-药物相互作用的可能性。
Objective： To establish a stable and efficient experimental model using primary rat hepatocyte and cyropreserved human hepatocyte so as to study the induction of small molecule compound SPH0396 to CYP1A2 and CYP3A4.Methods： The enzyme activity was evaluated using probe substrates metabolite. Results： SPH0396 had no effect on CYP3A4 at the concentrations of 0.1 ~ 3 mmol/L, suggesting that SPH0396 is not an inducer of CYP3A4. However, significant induction of CYP1A2 was observed at 3 mmol/L of SPH0396 and the induction reached more than two times. There is no difference between rat and human hepatocytes. Conclusion： SPH0396 may cause drug-drug interaction via induction of CYP1A2 and attention should be paid in clinic to the potential of drug-drug interaction resulting from its induction to CYP1A2.
出处
《上海医药》
CAS
2015年第19期71-75,共5页
Shanghai Medical & Pharmaceutical Journal
关键词
酪氨酸激酶抑制剂
肝细胞
诱导
tyrosine kinase inhibitors
hepatocyte
induction
