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硝苯地平骨架型缓释微丸在大鼠体内药代动力学及其与CYP3A4代谢酶活性的关系

张瑞卿, 杨文倩, 余裕炳, 涂家生, 孙益新

张瑞卿, 杨文倩, 余裕炳, 涂家生, 孙益新. 硝苯地平骨架型缓释微丸在大鼠体内药代动力学及其与CYP3A4代谢酶活性的关系[J]. 中国药科大学学报, 2018, 49(4): 427-432. DOI: 10.11665/j.issn.1000-5048.20180407
引用本文: 张瑞卿, 杨文倩, 余裕炳, 涂家生, 孙益新. 硝苯地平骨架型缓释微丸在大鼠体内药代动力学及其与CYP3A4代谢酶活性的关系[J]. 中国药科大学学报, 2018, 49(4): 427-432. DOI: 10.11665/j.issn.1000-5048.20180407
ZHANG Ruiqing, YANG Wenqian, YU Yubing, TU Jiasheng, SUN Yixin. Pharmacokinetics of nifedipine matrix sustained-release pellets in rats and the relationship with CYP3A4[J]. Journal of China Pharmaceutical University, 2018, 49(4): 427-432. DOI: 10.11665/j.issn.1000-5048.20180407
Citation: ZHANG Ruiqing, YANG Wenqian, YU Yubing, TU Jiasheng, SUN Yixin. Pharmacokinetics of nifedipine matrix sustained-release pellets in rats and the relationship with CYP3A4[J]. Journal of China Pharmaceutical University, 2018, 49(4): 427-432. DOI: 10.11665/j.issn.1000-5048.20180407

硝苯地平骨架型缓释微丸在大鼠体内药代动力学及其与CYP3A4代谢酶活性的关系

基金项目: 国家自然科学基金资助项目(No.81501579);国家科技重大专项资助项目(No.2017ZX09101001-005-003)

Pharmacokinetics of nifedipine matrix sustained-release pellets in rats and the relationship with CYP3A4

  • 摘要: 考察自制硝苯地平骨架型缓释微丸在大鼠体内药代动力学行为,并研究其与CYP3A4代谢酶活性的关系。首先建立用于CYP3A4活性测定的梯度洗脱高效液相色谱法,同时测定大鼠尿中的6β-羟基氢化可的松(6β-OHF)和氢化可的松(FC)含量;以尿液中6β-OHF和FC之比作为活性指标。以FC为探针,测定10只大鼠体内的CYP3A4酶活性;然后建立硝苯地平大鼠体内的分析测定方法,以市售硝苯地平片为参比制剂进行大鼠体内药物动力学研究;同时研究CYP3A4酶活性与硝苯地平大鼠体内药代动力学性质的关系。研究结果显示,10只大鼠CYP3A4酶活性为0.271±0.129;自制硝苯地平骨架型缓释微丸cmax显著降低约70%,tmax显著增加约400%、t1/2和MRT增加约230%,AUC0-∞无显著差异。硝苯地平缓释微丸与市售制剂相比,在大鼠体内具有明显的缓释效果,且CYP3A4酶活性会影响其药代动力学行为。
    Abstract: To conduct the characterization of its pharmacokinetics in rats of nifedipine sustained-release pellets and to study the relationship between the pellets and CYP3A4 activity. A gradient HPLC method was developed to simultaneously determine 6β-hydroxycortisol and hydrocortisone. CYP3A4 activity of rats was quantified by urinary ratio of 6β-hydroxycortisol/hydrocortisone after intravenous injection of hydrocortisone as a biomarker. HPLC method was also developed to quantify the drug concentration in plasma of rats, and the studies of pharmacokinetics were performed after oral administration of single dose of two formulations: Nifedipine matrix sustained-release pellets and nifedipine tablet(using as control). The results showed that the ratio of ten rats was 0. 271±0. 129. cmax of nifedipine sustained-release pellets decreases by nearly 70%, tmax significantly increased by 400% and t1/2 and MRT significantly increased by 230% compared to control. Nifedipine sustained-release pellets had a significant sustained-release property compared to the control and CYP3A4 activity affected its pharmacokinetics behavior.
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  • 刊出日期:  2018-08-24

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