地塞米松注射液对大鼠细胞色素P4502D6的影响

Effect of dexamethasone sodium phosphate injection on the cytochrome P4502D6 in rat

目的观察地塞米松(激素类药物)注射液对大鼠细胞色素P4502D6(CYP2D6)亚型的影响。方法 SD大鼠,雌雄各半,随机分成2组,地塞米松组按50mg·kg-1尾静脉给药,对照组按10mL.kg-1尾静脉给生理盐水,给药7d后,每组给予氢溴酸右美沙芬注射液5mg·kg-1;按时间从大鼠眼静脉取血10次,血样处理后,用HPLC法同时测定大鼠血浆CYP2D6R探针药物右美沙芬及其代谢产物去甲右美沙芬浓度,用DAS2.0软件进行分析,求出其主要药代动力学参数。结果地塞米松组与对照组比较,对右美沙芬t1/2无显著性差异;而AUC0-t右美沙芬为(63.43±7.71)mg·mL-1.min,与对照组(41.07±4.63)mg.L-1.min比较有显著性差异(P<0.05)。结论地塞米松注射液对右美沙芬有一定诱导作用,可以促进合用药物的消除,从而加速其代谢。

Objective To study effect of CYP2D6 subtypes with dexamethasone sodium phosphate injection in rats.Methods A total of 12 SD rats were randomly divided into two groups：dexamethasone group（50 mg·kg-1）and normal saline group（10 mL·kg-1）,which were intravenous medication.After seven days,two groups were injected dextromethorphan（5 mg·kg-1）,then RP-HPLC method was used to determine the concentrations of dextromethorphan and dextrorphan in rats plasma at different time.Pharmacokinetic model and parameters were analyzed by Drug and Statistics（DAS 2.0）.Results There was significant difference in pharmacokinetic parameter AUC of dexamethasone sodium phosphate injection（63.43±7.71）mg·L-1·min and control group（41.07±4.63）mg·L-1·min and there was no significant difference in pharmacokinetic parameter t1/2 between the two groups.Conclusion Dexamethasone injection have induction to dextromethorphan,so it could promote elimination with combination drugs,which was enhance the metabolism effects.