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辛伐他汀对非洛地平在大鼠中的代谢和药代动力学的影响

阴新娟, 杨岩, 田媛, 田稷馨, 于沛, 张尊建

阴新娟, 杨岩, 田媛, 田稷馨, 于沛, 张尊建. 辛伐他汀对非洛地平在大鼠中的代谢和药代动力学的影响[J]. 中国药科大学学报, 2014, 45(4): 450-455. DOI: 10.11665/j.issn.1000-5048.20140412
引用本文: 阴新娟, 杨岩, 田媛, 田稷馨, 于沛, 张尊建. 辛伐他汀对非洛地平在大鼠中的代谢和药代动力学的影响[J]. 中国药科大学学报, 2014, 45(4): 450-455. DOI: 10.11665/j.issn.1000-5048.20140412
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YIN Xinjuan, YANG Yan, TIAN Yuan, TIAN Jixin, YU Pei, ZHANG Zunjian. Effect of simvastatin on the metabolism and pharmacokinetics of felodipine in rats[J]. Journal of China Pharmaceutical University, 2014, 45(4): 450-455. DOI: 10.11665/j.issn.1000-5048.20140412
Citation: YIN Xinjuan, YANG Yan, TIAN Yuan, TIAN Jixin, YU Pei, ZHANG Zunjian. Effect of simvastatin on the metabolism and pharmacokinetics of felodipine in rats[J]. Journal of China Pharmaceutical University, 2014, 45(4): 450-455. DOI: 10.11665/j.issn.1000-5048.20140412
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辛伐他汀对非洛地平在大鼠中的代谢和药代动力学的影响

  • 1.

    中国药科大学药物质量与安全预警教育部重点实验室

  • 2.

    天然药物活性组分与药效国家重点实验室

Effect of simvastatin on the metabolism and pharmacokinetics of felodipine in rats

摘要

    摘要
  • 摘要: 非洛地平和辛伐他汀在临床上广泛被联合使用，然而并未见关于二者相互作用的研究报道，本研究旨在从体内和体外两方面研究辛伐他汀对非洛地平的代谢和口服药代动力学的影响。非洛地平和辛伐他汀在大鼠肝微粒体中共温孵，结果表明辛伐他汀是非洛地平的非竞争性抑制剂，抑制常数Ki=(9.86±0.27)μmol/L。12只大鼠随机分为两组，Ⅰ组灌服非洛地平；Ⅱ组灌服非洛地平和辛伐他汀。大鼠同时灌服非洛地平和辛伐他汀后，测得非洛地平的cmax和AUC0-∞显著增加，清除率(CLz/F)显著降低，而平均驻留时间(MRT0-∞)和半衰期(t1/2)无显著性变化。结果表明辛伐他汀促进了非洛地平在大鼠体内的吸收。该实验为非洛地平和辛伐他汀可能存在的药物相互作用提供了理论参考。
    Abstract: Felodipine has been widely coadministered with simvastatin for the treatment of cardiovascular disease(CVD). However, in vitro and in vivo interactions between them have not been systemically understood. Herein, the effects of simvastatin on the in vitro metabolism and oral pharmacokinetic profile of felodipine were investigated. Felodipine was incubated in rat liver microsomes(RLMs)with or without simvastatin. Simvastatin was found to be a non-competitive inhibitor(inhibition constant(Ki): (9. 86±0. 27)μmol/L). Following oral combination of felodipine and simvastatin, the peak plasma concentration(cmax)and area under the plasma concentration-time curve(AUC0-∞)of felodipine increased significantly, and the clearance(CLz/F)decreased obviously, while the mean residence time(MRT0-∞)and biological half-life(t1/2)were not statistically different. The altered pharmacokinetic profile of felodipine was probably due to the promoting effect of simvastatin on felodipine absorption. These findings provide some useful information for possible drug-drug interactions(DDIs)in rats, which should be paid particular attention to when felodipine and simvastatin are coadministered in clinical.
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  • 刊出日期:  2014-08-24

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