地高辛联合氨氯地平对大鼠肝微粒体细胞色素P450的影响

目的研究地高辛合用氨氯地平对大鼠肝脏组织药物代谢酶活性的影响,探讨两药合用后对药物代谢的影响,为临床合理用药提供理论依据。方法雄性大鼠40只,随机均分为空白对照、地高辛、氨氯地平、地高辛+氨氯地平组,每天给药1次,7d后处死。分别测定细胞色素P450和细胞色素b5含量,丙氨酸氨基转移酶、红霉素N-脱甲基酶、氨基比林N-脱甲基酶和7-乙氧基香豆素脱烃酶的活性。结果灌胃给药7d,地高辛、氨氯地平及联合用药对红霉素N-脱甲基酶活性均有明显抑制作用,联合用药的抑制作用未见增强。结论地高辛与氨氯地平合用对细胞色素P450酶系抑制作用未见增强。

Effects of digoxin in combination with amlodipine on CYP450 in rat liver microsomes

Objective To study the total content and activity of cytochrome P450(CYP450) in rat liver induced by digoxin in combination with amlodipine,and to evaluate their availability and safety for rational administration in clinic.Methods Male rats were randomly administrated with drugs(0.5%CMC-Na,digoxin,amlodipine,digoxin co-administration with amlodipine) respectively for seven days,once a day.After seven days,the total content of CYP450 and the activities of aminopyrine-N-demethylase(ADM),erytheomycin-N-demethylase(ERD) and coumarin-7-hydroxylation were determined in liver,alanine aminotransferase(ALT) was studied in serum.Results Digoxin at 0.05 mg,amlodipine at 1.0 mg and co-administration of digoxin and amlodipine all had significant inhibitory effect on ERD,but it exhibited no inhibitory action on ADM and 7-CH after oral administration for seven days in rat.Compared with digoxin or amlodipine,co-administration of digoxin and amlodipine showed no more inhibitory effect on ERD.Conclusion Co-administration of digoxin and amlodipine showed no significant drug interaction,which not changing the drug efficacy and increasing incidence of adverse drug reaction.