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

王玉浩; 张雪; 周小庭; 何华; 柳晓泉

doi:10.11665/j.issn.1000-5048.20170109

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

中国药科大学药代研究中心

基金项目: 国家自然科学基金资助项目(No.81503145)

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- 刊出日期: 2017-02-24

Pharmacokinetic interaction between sunitinib and ramipril in rats

摘要

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。
- 舒尼替尼 /
- 雷米普利 /
- 药代动力学相互作用 /
- 联合用药 /
- LC-MS/MS
Abstract: The purpose of this study was to investigate the pharmacokinetic interaction between sunitinib and ramipril in rats. Eighteen male SD rats were divided into three groups, with each group being assigned to orally receive sunitinib, ramipril, sunitinib and ramipril, respectively, for ten days. Blood samples were collected at different times after first-day and tenth-day administration. The concentrations of ramiprilat and sunitinib in rat plasma were determined by LC/MS/MS and the pharmacokinetic parameters were calculated and statistically analyzed. Compared with the administration of ramipril alone, after a single-dose combined administration, t_max of ramiprilat decreased significantly and t_1/2 prolonged, while AUC_0-∞ remained unchanged. These results indicated that the absorption rate of ramiprilat increased and the elimination rate decreased, but total absorption degree was not changed. After multiple-dose administrations, CL of ramiprilat decreased and AUC_0-∞ increased obviously. It suggested that accumulation of ramiprilat occurred in body and the drug elimination became slower. No obvious difference of sunitinib pharmacokinetic behavior was found when it was given in combination with ramipril after a single-dose administration or multiple-dose administration. Sunitinib decreased the elimination of ramiprilat after co-administration in company with drug accumulation in body after multiple-dose co-administration. The study showed that there were pharmacokinetic interactions between sunitinib and ramipril in SD rats.
- sunitinib /
- ramipril /
- pharmacokinetic interaction /
- drug combination /
- LC/MS/MS

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参考文献(16)

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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

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出版历程

Pharmacokinetic interaction between sunitinib and ramipril in rats

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出版历程

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