肠道菌群变化对替格瑞洛在大鼠体内药代动力学的影响

发布时间：2018-06-06 03:54

  本文选题：替格瑞洛 + 高效液相色谱-串联质谱　； 参考：《中国临床药理学杂志》2017年07期

【摘要】：目的探究肠道菌群变化对替格瑞洛在大鼠体内药代动力学的影响。方法将45只SD大鼠随机分为对照组、实验A组和实验B组,分别灌胃予以等量蒸馏水、双歧杆菌乳杆菌三联活菌片0.8 g·kg~(-1)、阿莫西林克拉维酸钾片125 mg·kg~(-1),连续7 d。第8天,3组大鼠均予以替格瑞洛18 mg·kg~(-1),并于给药前和给药后0.08,0.25,0.50,1,1.5,2,3,4,6,8,12,24 h眼内眦取血,用LC-MS/MS法测定血药浓度。用DAS 2.1.1软件拟合药代动力学参数,用SPSS21.0软件对药代动力学参数进行统计分析。结果实验A组、实验B组和对照组替格瑞洛的主要药代动力学参数如下:AUC_(0-t)分别为(6336.24±1840.46),(4444.05±1033.43),(4469.32±928.47)ng·mL~(-1)·h;AUC_(0-∞)分别为(6841.98±1975.95),(4656.66±1083.78),(4736.47±897.42)ng·mL~(-1)·h~(-1);C_(max)分别为(858.65±275.98),(648.81±215.59),(617.49±168.95)ng·mL~(-1);t_(1/2)分别为(6.40±2.18),(5.25±1.39),(5.68±2.08)h;t_(max)分别为(0.88±0.23),(0.90±0.21),(1.30±0.59)h;清除率分别为(2.82±0.72),(4.07±0.99),(3.95±0.91)L·h~(-1)·kg~(-1);表观分布容积分别为(26.07±12.00),(31.45±14.65),(32.95±14.17)L·kg~(-1)。实验A组与对照组的AUC_(0-t)、AUC_(0-∞)、C_(max)、t_(max)和清除率比较差异均有统计学意义(P0.05);实验B组与对照组的药代动力学参数比较,差异均无统计学意义(P0.05)。结论肠道益生菌增加会使替格瑞洛的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. 缁撴灉瀹為獙A缁，

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