Pharmacokinetic interaction between sunitinib and ramipril in rats
10.11665/j.issn.1000-5048.20170109
- VernacularTitle: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
- Author:
Yuhao WANG
;
Xue ZHANG
;
Xiaoting ZHOU
;
Hua HE
;
Xiaoquan LIU
- Keywords:
sunitinib;
ramipril;
pharmacokinetic interaction;
drug combination;
LC/MS/MS
- From:
Journal of China Pharmaceutical University
2017;48(1):60-65
- CountryChina
- Language:Chinese
-
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 dif-ferent 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, tmax of ramiprilat decreased significantly and t1/2 prolonged, while AUC0-∞ remained unchanged. These results indicated that the ab-sorption 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 AUC0-∞ increased obviously. It sug-gested 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.
