CAJ | 학술논문

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CYP 3A4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0.1 mmol/L和1mmol/L对CYP酶（1A2和3A4）无诱导作用，3mmol/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。
목적：건립은정고효적원대대서간세포화동존인간세포유도실험모형，연구SPH0396대CYP1A2화CYP 3A4적유도。방법：이용탐침저물대사물생성량대CYP3A4화CYP1A2적매활성진행평개。결과：SPH0396재0.1 mmol/L화1mmol/L대CYP매（1A2화3A4）무유도작용，3mmol/L시대CYP 3A4무유도，이대CYP1A2적유도배수균대우2，초보인위기유도CYP1A2,차유도작용재원대대서여동존인간세포중무충속차이。결론：SPH0396능유도CYP1A2，수관주SPH0396인유도CYP1A2이도치림상상발생약물-약물상호작용적가능성。
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 0.1~3mmol/L, suggesting that SPH0396 is not an inducer of CYP3A4. However, signiifcant induction of CYP1A2 was observed at 3mmol/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.