三七提取物对大鼠体内他莫昔芬及其代谢物的药动学的影响

目的:研究三七提取物对大鼠体内他莫昔芬及其代谢物的药动学的影响。方法:口服给予大鼠三七提取物10 d后再分别予口服、静注他莫昔芬,采用LC-MS/MS方法,测定他莫昔芬和4-羟基他莫昔芬在血浆和胆汁中的浓度,比较药动学行为的改变情况。结果:三七提取物未改变他莫昔芬及其代谢物的血浆药动学参数,但能明显影响他莫昔芬及其代谢物的口服吸收和胆汁排泄。结论:三七提取物对大鼠体内他莫昔芬及其代谢物的口服吸收和胆汁排泄存在影响,临床上二者合用时应注意潜在的药物相互作用。

Effects of Panax notoginseng extract on pharmacokinetics of tamoxifen and its metabolite in rats

OBJECTIVE To study the effects of Panax notoginseng extract on pharmacokinetics of tamoxifen and its metabolite in rats. METHODS Concentrations of tamoxifen and 4-hydroxytamoxifen in rat plasma and bile were determined by LC-MS/MS after 10 days of pretreatment of Panax notoginseng extract and then after oral or intravenous administration of tamoxifen to rats. Influences of Panax notoginseng extract on pharmacokinetics, oral bioavailability and biliary excretion of tamoxifen and 4-hydroxytamoxifen were investigated. RESULTS Pretreatment of Panax notoginseng extract did not alter plasma pharmacokinetics of tamoxifen or 4-hydroxytamoxifen, but it could significantly affect oral absorption and biliary excretion of both tamoxifen and its metabolite, 4-hydroxytamoxifen.CONCLUSION Panax notoginseng extract has influences on oral absorption and biliary excretion of tamoxifen and 4-hydroxytamoxifen in rats. Attentions should be paid when tamoxifen and 4-hydroxytamoxifen are combined.