摘要
目的:建立生物样本中测定呱氨托美汀(MED-15)及其代谢产物浓度的方法,考察MED-15在人工体液中的稳定性及在大鼠体内的组织分布。方法:制备人工胃液和人工肠液,考察MED-15在体液中的稳定性。取24只雄性SD大鼠,灌胃给药MED-15 100 mg·kg-1,分别于给药后1,3,7,24 h处死大鼠,迅速取出心脏、脑组织、肺脏、肝脏、肾脏、脾脏、胃、小肠和大肠匀浆,HPLC法检测各组织中MED-15、MED-5及托美汀的含量。结果:MED-15在人工胃液和肠液中的稳定时间>3 h。灌胃给予MED-15(100 mg·kg-1)后,MED-15仅在胃、大肠和小肠中可测得,并且肠道滞留时间长达24 h。代谢产物MED-5在大鼠体内多个组织均有分布,在胃、小肠、大肠和肝脏等组织中的浓度较高,7 h后在小肠和大肠中仍可检测到较高浓度的MED-5。MED-15活性代谢产物托美汀在肝、脾、肾等血流量丰富的组织中分布迅速而广泛,同时在这些组织中浓度较高。结论:呱氨托美汀可缓慢吸收入血,其在胃肠上皮细胞中滞留的现象也可能是其发挥作用时间较长的原因之一。
OBJECTIVE To establish an HPLC method for the determination of amtolmetin guacil （MED-15） and its metabolite in rat biological samples, and to investigate the stability of MED-15 in artificial fluid and characteristics of tissue distribution. METHODS Artificial gastric juice and artificial intestinal fluid were prepared to investigate the stability of MED-15 in the aritifical body fluids. A total of 24 SD male rats were administered with a single dose of 100mg.kg^-1 （ig）, and then the concen- trations of MED-15, MED-5 and tolmetin in heart, brain tissue, lung, liver, kidney, spleen, stomach, small intestine and large intestine were deiermined. RESULTS MED-15 was stable in artificial gastric juice and artificial intestinal fluid for more than 3 h. MED-15 existed only in stomach, small intestine and large intestine and residented in the intestine for as long as 24 h. MED-5 was found in many tissues and higher levels were found in the stomach, small intestine and large intestine. The active metabolite tolmetin of MED-15 was rapidly and widely distributed in the liver, spleen, kidney and other tissues which are rich in blood flow. CONCLUSION Amtolmetin guacil can be slowly absorbed into the bloodstream, and the phenomenon of retention in the gastrointestinal epithelial cells may also be one of the reasons for its longer efficacy.
出处
《中国医院药学杂志》
CAS
CSCD
北大核心
2014年第24期2120-2124,共5页
Chinese Journal of Hospital Pharmacy
