黛力新及其组分对大鼠体内他莫昔芬及其代谢物的药动学影响  

The pharmacokinetic effects of Deanxit and its components on tamoxifen and its metabolites in rat

作　　者：陈舒 王鹏[1] Chen Shu

机构地区：[1]浙江省金华市人民医院,321000

出　　处：《浙江临床医学》2022年第6期818-821,825,共5页Zhejiang Clinical Medical Journal

基　　金：金华市科学技术局公益类项目(2019-4-048);浙江省药学会医院药学专项科研资助项目(2018ZYY61)。

摘　　要：目的探讨黛力新与其组分氟哌噻吨、美利曲辛在大鼠体内对他莫昔芬及其代谢物的药动学影响。方法将20只雌性SD大鼠随机分为他莫昔芬组、他莫昔芬+氟哌噻吨组(0.21 mg/kg)、他莫昔芬+美利曲辛组(4.21 mg/kg)和他莫昔芬+黛力新组(氟哌噻吨0.21 mg/kg+美利曲辛4.21 mg/kg),每组各5只。通过尾静脉采血法采血,使用蛋白沉淀法处理生物样本,采用超高液相色谱-串联质谱(UPLC-MS/MS)法测定大鼠血浆中他莫昔芬及其代谢产物的含量,使用药动学软件求算药动学参数,通过比较药动学参数变化来评估黛力新及其组分对大鼠体内他莫昔芬代谢的影响。结果与他莫昔芬对照组比较,氟哌噻吨能显著降低他莫昔芬和N-去甲基他莫昔芬的AUC和C_(max),增加CL_(z)/F。美利曲辛能显著增加N-去甲基他莫昔芬的CL_(z)/F和V_(z)/F。黛力新能显著降低他莫昔芬的C_(max),同时能显著降低N-去甲基他莫昔芬AUC(0-t)。结论黛力新对他莫昔芬的代谢过程有一定的诱导作用,黛力新与他莫昔芬联用治疗乳腺癌患者的抑郁症从药物代谢角度来看不存在安全性问题。Objective To study the pharmacokinetic effects of tamoxifen and its metabolites in rats with Deanxit and its components,flupentixol and melitracen.Methods A total of twenty female Sprague-Dawley(SD)rats were randomly and evenly divided into four groups,Tamoxifen control group,Tamoxifen+Flupentixol group(Flupentixol 0.21 mg/kg),Tamoxifen+Melitracen group(Melitracen 4.21 mg/kg)and Tamoxifen+Deanxit group(Flupentixol 0.21 mg/kg+Melitracen 4.21 mg/kg),with 5 rats in each group.The plasma samples were collected from the tail vein.Plasma samples were extracted by protein precipitation.The ultra-high performance liquid hromatography-mass spectrometry method(UPLC-MS/MS)was used to detect the content of tamoxifen and its metabolites.The concentration-time data was processed by the pharmacokinetic calculation program to calculate the pharmacokinetic parameters.The comparison of pharmacokinetic parameters were used to evaluate the differences in tamoxifen metabolism in vivo between Deanxit and its components.Results Compared with control group,the AUC and C_(max) of tamoxifen or N-desmethyl tamoxifen in Tamoxifen+Flupentixol group were all significantly decreased,then their CL_(z)/F were all significantly increased.Melitracen increased CL_(z)/F and V_(z)/F of N-desmethyl tamoxifen.Deanxit decreased C_(max) of tamoxifen and AUC(0-t)of N-desmethyl tamoxifen.Conclusion Deanxit could induce tamoxifen metabo lism slightly.Coadministration of Deanxit with ta moxifen has no safety issues in breast cancer patient with th e depression.

关 键 词：他莫昔芬 氟哌噻吨 美利曲辛 黛力新 药物相互作用 药代动力学 

分 类 号：R28[医药卫生—中药学]