摘要
通过Beagle犬及人肝微粒体体外试验评价抗寄生虫化合物9901低、中、高剂量(7.5、30和60mg/kg)对肝细胞色素P450同工酶1A2、3A4、2A6和2D6的作用。用HPLC法测定非那西丁、睾酮、香豆素和右美沙芬经微粒体酶代谢所得产物的生成量以评价酶活。犬肝微粒体试验结果显示,化合物9901对CYP1A2和CYP3A4无诱导或抑制作用。人肝微粒体体外试验表明,化合物9901浓度小于200μg/L时,对CYP1A2、2A6、2D6和3A4均没有诱导或抑制作用,提示其在联合用药时较安全。
The effects of an anti-parasitic compound 9901 with low, middle and high dosages （7.5, 30 and 60mg/kg） on cytochrome P450 （CYP450） were evaluated by using Beagle dog liver mcirosomes ex vivo and human liver microsomes in vitro. The content of metabolic products of four drugs--acetophenetidin, testosterone, coumarin and dextromethorphan were determined by HPLC in order to evaluate the enzyme activity. The results showed that the compound 9901 had no inductive or inhibitive effect on the activities of CYP1A2 and CYP3A4 in dog liver microsomes after oral administration for 4 weeks. In vitro results showed the compound 9901 had no significant effect on the activities of CYP1A2, CYP2A6, CYP2D6 and CYP3A4 in human liver microsomal incubations when its concentration was below 200μg/L. The results indicated that the compound 9901 was relatively secure in drug combination.
出处
《中国医药工业杂志》
CAS
CSCD
北大核心
2008年第1期31-35,49,共6页
Chinese Journal of Pharmaceuticals
