TCM  >> Vol. 6 No. 2 (May 2017)

    五酯胶囊对肾移植术后早期他克莫司药代动力学和肝肾功能的影响
    Effect of Wuzhi Capsule on the Pharmacokinetics and Liver Function, Renal Function of Tacrolimus

  • 全文下载: PDF(740KB) HTML   XML   PP.98-103   DOI: 10.12677/TCM.2017.62017  
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作者:  

雷慧君,罗颖鎏,苏 蟠,李晶晶,武鹏浩,李慧青,王 添,路 静,杨万雷:郑州大学基础医学院,河南 郑州

关键词:
五酯胶囊他克莫司药代动力学肝功能肾功能Wuzhi Capsule Tacrolimus Pharmacokinetics Liver Function Renal Function

摘要:

目的:五味子,木兰科的多年生草本植物北五味子属的成熟果实,其在许多国家广泛用作滋补类营养品和恢复性加强肝脏及其他器官的功能。五酯胶囊,一种五味子醇提制剂,是一个著名的中药,在中国广泛使用。五酯胶囊及其活性成分木酚素/木脂素显著保护肝损伤,在中国通常与TAC联合应用来防止药物引起的肝炎。本研究旨在探讨五酯胶囊对肾移植术后早期他克莫司血药浓度和肝肾功能的影响。方法:回顾性研究113名肾移植受者,未用五酯胶囊者55人,匹配年龄和性别后应用五酯胶囊者58人,所有患者接受Tac + MMF + Pred三联免疫抑制治疗。检测3天、7天和30天时Tac的血药浓度的变化,使用微粒酶免疫测定(MEIA)法。与此同时,测试所有患者的肝脏、肾脏功能。肝功能、肾功能、全血他克莫司浓度进行了两组之间的分析比较。结果:我们发现五酯胶囊可以显著提高3天、7天和30天时TAC血药浓度。3天、7天和30天时,五酯胶囊组全血Tac浓度平均增加了40.1%、23.3%、15.0%。更重要的是,直接胆红素也显著降低。两组之间其他的肝肾功能指标没有显著的差异(P > 0.05)。结论:五酯胶囊可以显著提高肾移植受者的Tac血药浓度,且具有保护肝脏的作用,没有明显的不良反应。

Objective: Fructus Schisandrae, the ripe fruits of perennial plant of Schisandra chinensis (Turcz.) Baill, perennial herb of family Magnoliaceae, is widely used as a restorative, tonic nutrition to enhance the function of liver and other organs in many countries. Wuzhi capsule, an ethanol extract preparation of Fructus Schisandrae, is a well-known herbal medicine widely used in China. Wuzhi capsule and its active lignans significantly protect liver injury, and are often prescribed with TAC to prevent drug-induced hepatitis in China. This study aimed to investigate the effects of Wuzhi capsule on blood concentration of tacrolimus and liver function, renal function after renal transplantation. Methods: One hundred and thirteen renal transplant recipients were randomly assigned to two groups, i.e., 58 in the WC group and 55 in the control group. All patients received Tac + MMF + Pred triple immunosuppressive therapy. One month was taken as one therapeutic course. Changes of the blood concentration of Tac were detected 3, 7, 30 d after medication in the two groups using microparticle enzyme immune assay (MEIA). Meanwhile, the liver and kidney functions were tested. Liver function, renal function, and whole-blood concentrations of tacrolimus were analyzed to compare between the two groups. Results: We found that WZ capsule could significantly increase TAC blood concentration at 3, 7, 30 d. At 3, 7, 30 d after the application of WC capsule, the blood Tac concentration increased 40.1%, 23.3%, 15.0% averagely. More importantly, serum DBIL was also remarkably reduced. There was no significant difference in the liver and renal functions between the two groups (P > 0.05). Conclusion: WC capsule could significantly increase the blood Tac concentration of renal transplant recipients with liver protection, and has no obvious adverse reaction.

文章引用:
雷慧君, 罗颖鎏, 苏蟠, 李晶晶, 武鹏浩, 李慧青, 王添, 路静, 杨万雷. 五酯胶囊对肾移植术后早期他克莫司药代动力学和肝肾功能的影响[J]. 中医学, 2017, 6(2): 98-103. https://doi.org/10.12677/TCM.2017.62017

参考文献

[1] Christians, U., Jacobsen, W., Benet, L.Z., et al. (2002) Mechanism of Clinically Relevant Drug Interactions Associated with Tacrolimus. Clinical Pharmacokinetics, 41, 813-851.
https://doi.org/10.2165/00003088-200241110-00003
[2] Iwaski, K. (2007) Metabolism of Tacrolimus (FK506) and Recent Topics in Clinical Pharmacokinetics. Drug Metabolism and Pharmacokinetics, 22, 328-335.
https://doi.org/10.2133/dmpk.22.328
[3] Wakasugi, H., Yano, I., Ito, T., et al. (1998) Effect of Clarithromycin on Renal Excretion of Digoxin: Interaction with P-Glycoprotein. Clinical Pharmacology & Therapeutics, 64, 123-128.
[4] Greiner, B., Eichelbaum, M., Fritz, P., et al. (1999) The Role of Intestinal P-Glycoprotein in the Interaction of Digoxin and Rifampin. Journal of Clinical Investigation, 104, 147-153.
https://doi.org/10.1172/JCI6663
[5] Park, J.Y., Shin, H.K., Choi, Y.W., et al. (2009) Gomisin A Induces Ca2+-Dependent Activation of eNOS in Human Coronary Artery Endothelial Cells. Journal of Ethnopharmacology, 125, 291-296.
[6] Park, J.Y., Shin, H.K., Lee, Y.J., et al. (2009) The Mechanism of Vasorelaxation Induced by Schisandra chinesis Extract in Rat Thoracic Aorta. Journal of Ethnopharmacology, 121, 69-73.
[7] Chiu, P.Y., Tang, M.H., Mak, D.H., et al. (2003) Hepatoprotective Mechanism of Schisandrin B: Role of Mitochondrial Glutathione Antioxidant Status and Heat Shock Proteins. Free Radical Biology & Medicine, 35, 368-380.
[8] Yan, F., Zhang, Q.Y., Jiao, L., et al. (2009) Synergistic Hepatoprotective Effect of Schisandrae lignans with Astragalus Polysaccharides on Chronic Liver Injury in Rats. Phytomedicine, 16, 805-813.
[9] Huang, F., Xiong, Y., Xu, L., et al. (2007) Sedative and Hypnotic Activities of the Ethanol Fraction from Fructus Schisandrae in Mice and Rats. Journal of Ethnopharmacology, 110, 471-475.
[10] Huang, X., Song, F., Liu, Z., et al. (2007) Studies on Lignin Constituents from Schisandra chinensis (Turcz.) Baill. Fruits Using High-Performance Liquid Chromatography/Electrospray Ionization Multiple-Stage Tandem Mass Spectrometry. Mass Spectrom, 42, 1148-1161.
https://doi.org/10.1002/jms.1246
[11] Xiao, W.L., Huang, S.X., Wang, R.R., et al. (2008) Nortriterpenoids and Lignans from Schisandra sphenanthera. Phytochemistry, 69, 2862-2866.
[12] Xu, M., Wang, G., Xie, H., et al. (2005) Determination of Schizandrin in Rat Plasma by High-Performance Liquid Chromatography-Mass Spectrometry and Its Application in Rat Pharmacokinetic Studies. Journal of Chromatography, B, Analytical Technologies in the Biomedical and Life Sciences, 828, 55-61.
[13] 谢申平, 晏强, 陈怀周, 等. 五酯胶囊在肾移植术后的临床应用研究[J]. 中国中西医结合杂志, 2011, 31(9): 1213- 1215.
[14] 辛华委, 李馨, 吴笑春, 等. 五酯胶囊与他克莫司合用对肾移植受者的成本与效果评估研究[J]. 中国临床药理学杂志, 2011, 27(4): 295-298.
[15] 郭晓伟, 陈刚, 朱兰, 等. 五酯胶囊对肾移植受者他克莫司血药浓度的影响[J]. 华中技大学学报(医学版), 2011, 40(1): 95-97.
[16] 蒋进发, 魏思东, 陈国勇. 五酯胶囊对肝移植受者他克莫司浓度的影响[J]. 中国临床药理学杂志, 2012, 28(6): 411-413.
[17] 吴静. 他克莫司联合五酯软胶囊治疗膜性肾病的临床观察[D]: [硕士学位论文]. 河南: 河南中医学院, 2013.
[18] Adam, R., Karam, V., Delvart, V., et al. (2015) Improved Survival in Liver Transplant Recipients Receiving Prolonged-Release Tacrolimus in the European Liver Transplant Registry. American Journal of Transplantation, 15, 1267-1282.
https://doi.org/10.1111/ajt.13171
[19] Souto-Rodriguez, R., Molina-Perez, E., Castroagudin, J.F., et al. (2014) Differences in the Incidence and Clinical Evolution of Early Neurotoxicity after Liver Transplantation Based on Tacrolimus Formulation Used in the Immunosuppressive Induction Protocol. Transplantation Proceedings, 46, 3117-3120.
[20] Thölking, G., Fortmann, C., Koch, R., et al. (2014) The Tacrolimus Metabolism Rate Influences Renal Function after Kidney Transplantation. PLoS ONE, 9, e111128.
https://doi.org/10.1371/journal.pone.0111128
[21] 陈夏, 蔡宪安. 五酯软胶囊在肾移植术后应用的临床研究(附60例报告)[J]. 器官移植, 2011, 2(5): 283-286.
[22] 朱兰, 王彼啸, 李娟, 等. 长期服用五酯胶囊减少他克莫司剂量对肾移植受者他克莫司药动学的影响[J]. 中华器官移植杂志, 2014, 35(9): 533-536.
[23] Iwata, H., Tezuka, K., Kadol, S., et al. (2004) Identification and Characterization of Potent CYP3A4 Inhibitors in Schisandra Fruit Extract. Drug Metabolism & Disposition, 32, 1351-1358.
https://doi.org/10.1124/dmd.104.000646
[24] 张明华, 陈虹, 李灵芝, 等. 五味子甲素和五味子醇甲对四氯化碳所致肝脏损伤的保护作用[J]. 武警医学, 2002, 13(7): 395-396.