舒尼替尼和雷米普利联合用药在大鼠体内的药代动力学相互作用

发布时间：2018-01-30 17:53

  本文关键词： 舒尼替尼 雷米普利 药代动力学相互作用 联合用药 LC-MS/MS　出处：《中国药科大学学报》2017年01期 　论文类型：期刊论文

【摘要】：初步考察舒尼替尼和雷米普利联合用药在大鼠体内的药代动力学相互作用。18只雄性SD大鼠随机分成3组,分别灌胃给予舒尼替尼、雷米普利、舒尼替尼合用雷米普利,连续给药10 d,分别于给药第1天和第10天后不同时间点采集血样,用LC-MS/MS测定雷米普利拉和舒尼替尼的血药浓度,并计算二者药代动力学参数。单剂量联合用药时,与单用雷米普利相比,合用舒尼替尼后,雷米普利拉t_(max)显著减小,t_(1/2)显著增加,AUC_(0-∞)没有显著性差异,表明其吸收加快,消除减慢,但整体吸收程度不变。多剂量给药后,联合用药组雷米普利拉CL显著降低、AUC_(0-∞)显著增大,表明联合用药导致雷米普利拉在大鼠体内消除减慢,并有明显的蓄积。单剂量和多剂量联合用药后舒尼替尼的药代动力学行为都没有发生显著变化。结果显示,舒尼替尼和雷米普利联合用药后会导致雷米普利拉消除减慢,并且单剂量联合用药后其吸收变快,多剂量联合用药后其在体内有明显蓄积,提示二者存在一定的药代动力学相互作用。
[Abstract]:To investigate the pharmacokinetic interaction of sulnitinib and ramipril in rats. Eighteen male SD rats were randomly divided into 3 groups and were given sulnitinib and ramipril respectively. The blood samples were collected at different time points on the 1st day and the 10th day after the administration of sulnitinib combined with Ramipril for 10 days. LC-MS/MS was used to determine the plasma concentrations of Ramiprar and sunitinib, and the pharmacokinetic parameters were calculated. When combined with single dose, compared with the single dose of Ramipril, the combination of sulmitinib and sulnitinib was used. There was no significant difference in the number of AUC _ 0-鈭，

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