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WANG Yuhao, ZHANG Xue, ZHOU Xiaoting, HE Hua, LIU Xiaoquan. Pharmacokinetic interaction between sunitinib and ramipril in rats[J]. Journal of China Pharmaceutical University, 2017, 48(1): 60-65. DOI: 10.11665/j.issn.1000-5048.20170109
Citation: WANG Yuhao, ZHANG Xue, ZHOU Xiaoting, HE Hua, LIU Xiaoquan. Pharmacokinetic interaction between sunitinib and ramipril in rats[J]. Journal of China Pharmaceutical University, 2017, 48(1): 60-65. DOI: 10.11665/j.issn.1000-5048.20170109

Pharmacokinetic interaction between sunitinib and ramipril in rats

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  • 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, tmax of ramiprilat decreased significantly and t1/2 prolonged, while AUC0-∞ 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 AUC0-∞ 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.
  • [1]
    Chu TF,Rupnick MA,Kerkela R,et al.Cardiotoxicity associated with tyrosine kinase inhibitor sunitinib[J].Lancet,2007,370(9604):2011-2019.
    [2]
    Kappers MH,Smedts FM,Horn T,et al.The vascular endothelial growth factor receptor inhibitor sunitinib causes a preeclampsia-like syndrome with activation of the endothelin system[J].Hypertension,2011,58(2):295-302.
    [3]
    Lankhorst S,Kappers MH,van Esch JH,et al.Treatment of hypertension and renal injury induced by the angiogenesis inhibitor sunitinib:preclinical study[J].Hypertension,2014,64(6):1282-1289.
    [4]
    Izzedine H,Derosa L,Le Teuff G,et al.Hypertension and angiotensin system inhibitors:impact on outcome in sunitinib-treated patients for metastatic renal cell carcinoma[J].Ann Oncol,2015,26(6):1128-1133.
    [5]
    McKay RR, Rodriguez GE, Lin X, et al. Angiotensin system inhibitors and survival outcomes in patients with metastatic renal cell carcinoma[J].Clin Cancer Res,2015,21(11):2471-2479.
    [6]
    Meisel S,Shamiss A,Rosenthal T.Clinical pharmacokinetics of ramipril[J].Clin Pharmacokinet,1994,26(1):7-15.
    [7]
    Franklin PH,Banfor PN,Tapang P,et al.Effect of the multitargeted receptor tyrosine kinase inhibitor,ABT-869[N-(4-(3-Amino-1H-indazol-4-yl)phenyl)-N ′-(2-fluoro-5-methylphenyl)urea],on blood pressure in conscious rats and mice:reversal with antihypertensive agents and effect on tumor growth inhibition[J].J Pharmacol Exp Ther,2009,329(3):928-937.
    [8]
    Belcik JT,Qi Y,Kaufmann BA,et al.Cardiovascular and systemic microvascular effects of anti-vascular endothelial growth factor therapy for cancer[J].J Am Coll Cardiol,2012,60(7):618-625.
    [9]
    Yusuf S,Sleight P,Pogue J,et al.Effects of an angiotensin-converting-enzyme inhibitor,ramipril,on cardiovascular events in high-risk patients.The heart outcomes prevention evaluation study investigators[J].N Engl J Med,2000,342(3):145-153.
    [10]
    Li XN,Xu JA,Chen WL,et al.Pharmacokinetics and bioequivalence of domestic and imported ramipril tablets[J].Chin J Clin Pharm(中国临床药学杂志),2009,18(1):9-13.
    [11]
    Scripture CD,Figg WD.Drug interactions in cancer therapy[J].Nat Rev Cancer,2006,6(7):546-558.
    [12]
    Jiang YQ,Tang QF,Zhang S,et al.Combined effects of gallic acid and ciprofloxacin on the murine chronic rhinosinusitis model in mice[J].J China Pharm Univ(中国药科大学学报),2015,46(5):600-604.
    [13]
    Di Gion P,Kanefendt F,Lindauer A,et al.Clinical pharmacokinetics of tyrosine kinase inhibitors:focus on pyrimidines,pyridines and pyrroles[J].Clin Pharmacokineti,2011,50(9):551-603.
    [14]
    Xie SS,Jing XY,Liu XD.Role of intestinal cytochrome P450s in drug metabolism[J].J China Pharm Univ(中国药科大学学报),2010,41(2):186-192.
    [15]
    van Erp NP,Gelderblom H,Guchelaar HJ.Clinical pharmacokinetics of tyrosine kinase inhibitors[J].Cancer Treat Rev,2009,35(8):692-706.
    [16]
    FDA.Drug Databases:Altace(Ramipril).http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/019901s065lbl.pdf.
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