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目的体外研究二-(4-氯苯甲酰异羟肟酸)二正丁基合锡(DBDCT)在大鼠肝微粒体中的代谢及酶促动力学,并探讨参与其代谢的主要CYP450同工酶亚型。方法 优化二-(4-氯苯甲酰异羟肟酸)二正丁基合锡在大鼠肝微粒体中的孵育条件,并对其在不同酶源中的酶促动力学进行研究;通过体外抑制实验初步探讨参与二-(4-氯苯甲酰异羟肟酸)二正丁基合锡代谢的主要CYP450同工酶的亚型。结果 不同酶源代谢实验显示,苯巴比妥(PB)、地塞米松(Dex)诱导组和空白对照组比较有显著性差异,而β-萘黄酮(BNF)组和空白对照组无明显差异;抑制实验显示酮康唑对二-(4-氯苯甲酰异羟肟酸)二正丁基合锡的代谢有较强的抑制作用;结论二-(4-氯苯甲酰异羟肟酸)二正丁基合锡在大鼠肝微粒体中代谢较快,CYP3A在催化二-(4-氯苯甲酰异羟肟酸)二正丁基合锡代谢中起了主导作用,CYP2C9可能部分参与,而CYP1A对二-(4-氯苯甲酰异羟肟酸)二正丁基合锡的代谢无明显催化作用;提示二-(4-氯苯甲酰异羟肟酸)二正丁基合锡与经上述同工酶代谢的药物联合应用时,应注意药物之间相互作用的可能性。
OBJECTIVE To study the metabolism and enzymatic kinetics of di-n-butyltin (DBDCT) in rat liver microsomes in vitro and to explore the role of major CYP450 involved in its metabolism Anzyme subtype. Methods The conditions for the incubation of di-n-butyltin bis (2-chlorobenzoylhydroxamate) in rat liver microsomes were optimized and their enzymatic kinetics in different enzyme sources were studied. In vitro inhibition assay Preliminary study of the subtypes of major CYP450 isoenzymes involved in the di-n-butyltin in metabolism of di- (4-chlorobenzoylhydroxamic acid). Results Different enzyme metabolism experiments showed that there were significant differences between the induced group of phenobarbital (PB) and dexamethasone (Dex) and the blank control group, but there was no significant difference between the BNF group and the blank control group . Inhibition experiments showed that ketoconazole had a strong inhibitory effect on the metabolism of di-n-butyltin bis (4-chlorobenzoylhydroxamate). CONCLUSION Di- (4-chlorobenzoylhydroxy oxime) Acid) di-n-butyltin is rapidly metabolized in rat liver microsomes. CYP3A plays a leading role in the metabolism of di- (4-chlorobenzoyl hydroxamic acid) di-n-butyltin, and CYP2C9 May be partially involved, while CYP1A has no obvious catalytic effect on the metabolism of di- (4-chlorobenzoylhydroxamic acid) di-n-butyltin tin; it is suggested that bis (4-chlorobenzoylhydroxamic acid) When n-butyltin is used in combination with drugs that are metabolized by the above isozymes, attention should be paid to the possibility of drug interactions.