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腸道菌群變化對(duì)替格瑞洛在大鼠體內(nèi)藥代動(dòng)力學(xué)的影響

發(fā)布時(shí)間:2018-06-06 03:54

  本文選題:替格瑞洛 + 高效液相色譜-串聯(lián)質(zhì)譜 ; 參考:《中國臨床藥理學(xué)雜志》2017年07期


【摘要】:目的探究腸道菌群變化對(duì)替格瑞洛在大鼠體內(nèi)藥代動(dòng)力學(xué)的影響。方法將45只SD大鼠隨機(jī)分為對(duì)照組、實(shí)驗(yàn)A組和實(shí)驗(yàn)B組,分別灌胃予以等量蒸餾水、雙歧桿菌乳桿菌三聯(lián)活菌片0.8 g·kg~(-1)、阿莫西林克拉維酸鉀片125 mg·kg~(-1),連續(xù)7 d。第8天,3組大鼠均予以替格瑞洛18 mg·kg~(-1),并于給藥前和給藥后0.08,0.25,0.50,1,1.5,2,3,4,6,8,12,24 h眼內(nèi)眥取血,用LC-MS/MS法測(cè)定血藥濃度。用DAS 2.1.1軟件擬合藥代動(dòng)力學(xué)參數(shù),用SPSS21.0軟件對(duì)藥代動(dòng)力學(xué)參數(shù)進(jìn)行統(tǒng)計(jì)分析。結(jié)果實(shí)驗(yàn)A組、實(shí)驗(yàn)B組和對(duì)照組替格瑞洛的主要藥代動(dòng)力學(xué)參數(shù)如下:AUC_(0-t)分別為(6336.24±1840.46),(4444.05±1033.43),(4469.32±928.47)ng·mL~(-1)·h;AUC_(0-∞)分別為(6841.98±1975.95),(4656.66±1083.78),(4736.47±897.42)ng·mL~(-1)·h~(-1);C_(max)分別為(858.65±275.98),(648.81±215.59),(617.49±168.95)ng·mL~(-1);t_(1/2)分別為(6.40±2.18),(5.25±1.39),(5.68±2.08)h;t_(max)分別為(0.88±0.23),(0.90±0.21),(1.30±0.59)h;清除率分別為(2.82±0.72),(4.07±0.99),(3.95±0.91)L·h~(-1)·kg~(-1);表觀分布容積分別為(26.07±12.00),(31.45±14.65),(32.95±14.17)L·kg~(-1)。實(shí)驗(yàn)A組與對(duì)照組的AUC_(0-t)、AUC_(0-∞)、C_(max)、t_(max)和清除率比較差異均有統(tǒng)計(jì)學(xué)意義(P0.05);實(shí)驗(yàn)B組與對(duì)照組的藥代動(dòng)力學(xué)參數(shù)比較,差異均無統(tǒng)計(jì)學(xué)意義(P0.05)。結(jié)論腸道益生菌增加會(huì)使替格瑞洛的C_(max)增加,AUC_(0-t)和AUC_(0-∞)增大清除率下降。
[Abstract]:Objective to investigate the effect of intestinal flora changes on the pharmacokinetics of tigrilol in rats. Methods Forty-five Sprague-Dawley rats were randomly divided into control group, experimental group A and experimental group B, respectively. The rats were given the same amount of distilled water by gavage, bifidobacterium Lactobacillus triple active bacteria tablet 0.8 g 路kg ~ (-1) and amoxicillin clavulanate potassium tablet 125 mg 路kg ~ (-1) ~ (-1) for 7 days. On the 8th day, the rats in the three groups were given tigrilol (18 mg / kg) and the blood concentration was determined by LC-MS/MS method before and after the administration. The pharmacokinetic parameters were fitted with DAS 2.1.1 software and the pharmacokinetic parameters were statistically analyzed by SPSS21.0 software. 緇撴灉瀹為獙A緇,

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