發(fā)布時(shí)間：2018-03-21 19:05

  本文選題：細(xì)胞色素P　切入點(diǎn)：混合探針底物法　出處：《中國(guó)藥學(xué)雜志》2015年10期 　論文類型：期刊論文

【摘要】：目的采用"Cocktail"探針?biāo)幬锓ǹ疾斓⒆⑸湟汉托目墒嫫瑢?duì)家兔CYP酶5種亞型CYP1A2、CYP2C9、CYP2C19、CYP2D6和CYP3A4代謝的影響。方法將16只雄性家兔同時(shí)空腹給予混合探針?biāo)幙Х纫�、甲苯磺丁脲、奧美拉唑、右美沙芬和咪達(dá)唑侖,采用LC-MS/MS檢測(cè)特定時(shí)間點(diǎn)的探針?biāo)幬锎x率(代謝產(chǎn)物濃度與探針原型藥物濃度的比值)。家兔隨機(jī)分為丹參注射液組和心可舒片組,設(shè)計(jì)為自身對(duì)照實(shí)驗(yàn),分3個(gè)周期,按順序分別給藥丹參低劑量組(0.5 m L·kg-1)、中劑量組(1 m L·kg-1)、高劑量組(2 m L·kg-1)和心可舒低劑量組(90 mg·kg-1)、中劑量組(180 mg·kg-1)和高劑量組(360 mg·kg-1)。每個(gè)周期經(jīng)7 d洗凈期后,連續(xù)給藥7 d,第15天再給予探針?biāo)幬锖鬁y(cè)代謝率。采用ANOVA方差分析比較各劑量組家兔和用藥前探針?biāo)幬锏拇x率的變化。結(jié)果與用藥前相比,各劑量組的混合探針?biāo)幬锎x率均有下降趨勢(shì)。結(jié)論丹參注射液、心可舒片使用7 d后可能抑制家兔體內(nèi)CYP450酶代謝,與體外實(shí)驗(yàn)結(jié)果一致。這些藥物與經(jīng)過CYP450酶代謝的藥物聯(lián)合應(yīng)用時(shí),可能會(huì)引起藥物相互作用,臨床聯(lián)合使用應(yīng)提高警惕。
[Abstract]:Objective to investigate the effects of Salvia miltiorrhiza injection and Xinkesu tablet on the metabolism of CYP2C19 CYP2D6 and CYP3A4 in five subtypes of CYP enzymes in rabbits by "Cocktail" probe method. Methods 16 male rabbits were treated with caffeine, tolbutylurea and omeprazole on an empty stomach. Dextromethorphan and midazolam were used to detect the metabolic rate of probe drug (the ratio of metabolite concentration to probe prototype drug concentration) at a specific time point by LC-MS/MS. Rabbits were randomly divided into Danshen injection group and Xinkesu tablet group. Three cycles were divided into three periods: Danshen low dose group (0.5 mg / kg -1), middle dose group (1 mg / kg -1), high dose group (2 mg / kg -1), Xinkesu low dose group (90 mg kg -1), medium dose group (180 mg kg -1) and high dose group (360 mg kg -1). ANOVA variance analysis was used to compare the changes of the metabolic rate of the probe drugs in rabbits and before and after the administration of the drug for 7 days, and the results were compared with those before the administration of the drug, and the results showed that the metabolic rate of the probe drug was higher than that of the control group before and after the administration of the drug. Conclusion Salvia miltiorrhiza injection and Xinkeshu tablet may inhibit the metabolism of CYP450 enzyme in rabbits after 7 days of treatment. These drugs may cause drug interaction when combined with drugs metabolized by CYP450 enzymes.
【作者單位】： 復(fù)旦大學(xué)附屬華山醫(yī)院藥劑科;復(fù)旦大學(xué)附屬華東醫(yī)院藥劑科;山東省千佛山醫(yī)院藥劑科;上海市徐匯區(qū)中心醫(yī)院中心實(shí)驗(yàn)室;
【分類號(hào)】：R965

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本文編號(hào)：1645145