留言板

尊敬的读者、作者、审稿人, 关于本刊的投稿、审稿、编辑和出版的任何问题, 您可以本页添加留言。我们将尽快给您答复。谢谢您的支持!

姓名
邮箱
手机号码
标题
留言内容
验证码

个体化给药辅助决策系统JPKD对肾移植受者他克莫司血药浓度预测能力评估

颜辉, 吴芙蓉, 季鹏, 等. 个体化给药辅助决策系统JPKD对肾移植受者他克莫司血药浓度预测能力评估[J]. 器官移植. doi: 10.3969/j.issn.1674-7445.2024011
引用本文: 颜辉, 吴芙蓉, 季鹏, 等. 个体化给药辅助决策系统JPKD对肾移植受者他克莫司血药浓度预测能力评估[J]. 器官移植. doi: 10.3969/j.issn.1674-7445.2024011
Yan Hui, Wu Furong, Ji Peng, et al. Evaluation of the predictive ability of individualized drug administration adjuvant decision-making system JPKD for tacrolimus blood concentration in kidney transplant recipients[J]. ORGAN TRANSPLANTATION. doi: 10.3969/j.issn.1674-7445.2024011
Citation: Yan Hui, Wu Furong, Ji Peng, et al. Evaluation of the predictive ability of individualized drug administration adjuvant decision-making system JPKD for tacrolimus blood concentration in kidney transplant recipients[J]. ORGAN TRANSPLANTATION. doi: 10.3969/j.issn.1674-7445.2024011

个体化给药辅助决策系统JPKD对肾移植受者他克莫司血药浓度预测能力评估

doi: 10.3969/j.issn.1674-7445.2024011
基金项目: 安徽省高等学校省级质量工程项目(2020jyxm2326)
详细信息
    作者简介:
    通讯作者:

    张圣雨(ORCID 0009-0002-2889-1047),硕士,主任药师,研究方向为临床药学,Email:zhangshengyu@126.com

  • 中图分类号: R617, R979.5

Evaluation of the predictive ability of individualized drug administration adjuvant decision-making system JPKD for tacrolimus blood concentration in kidney transplant recipients

More Information
  • 摘要:   目的   分析个体化给药辅助决策系统Java PK® for Desktop(JPKD)对肾移植受者他克莫司血药浓度的预测能力及影响因素。  方法  收集149例肾移植术后早期受者他克莫司血药浓度监测数据,使用JPKD预测他克莫司剂量调整后的血药谷浓度,计算实测浓度与预测浓度之间的绝对值权重偏差和相对预测误差。使用单因素和多因素logistic回归分析影响绝对权重偏差的相关因素,并绘制受试者工作特征(ROC)曲线评价影响因素对软件预测准确性的判断价值。  结果  收集149例患者266例次血药浓度数据,他克莫司血药浓度实测值为(6.5±3.0)ng/mL(1.1~16.6 ng/mL),JPKD进行计算的预测值为(5.6±2.5)ng/mL(1.4~14.4 ng/mL),计算结果的绝对权重偏差为28.38%,相对预测误差为−13.55%。单因素分析显示性别、白蛋白、红细胞比容变化、细胞色素P450(CYP)3A5*3基因型、C3435T基因型与预测结果不准确有关。多因素logistic回归分析显示CYP3A5*3基因型为AA、红细胞比容变化是影响JPKD预测他克莫司血药浓度准确性的独立危险因素。ROC曲线分析显示,红细胞比容变化>2.25%时,软件预测不准确的风险增加。  结论  JPKD用于预测肾移植受者他克莫司血药浓度具有一定的准确性,可以提高血药浓度的达标率,但CYP3A5*3基因型、红细胞比容变化会影响预测的准确性。

     

  • 图  1  红细胞比容变化评估JPKD软件预测他克莫司血药浓度准确性的ROC曲线

    Figure  1.  ROC curve of hematocrit value change to evaluate the accuracy of JPKD software in predicting tacrolimus blood concentration

    表  1  JPKD预测他克莫司血药浓度准确性的影响因素单因素分析

    Table  1.   Univariate analysis of factors affecting the accuracy of tacrolimus blood concentration predicted by JPKD

    指标 预测准确组(n=167) 预测不准确组(n=99) 统计值 P
    性别[n(%)] 1.852 0.174
     男 97(58) 49(49)
     女 70(42) 50(51)
    年龄[MP25,P75),岁] 34(30,41) 33(27,41) −1.024 0.306
    身高($\overline x \pm s $,cm) 165±8 164±7 0.789 0.431
    体质量[MP25,P75),kg] 56(51,63) 55(50,60) −1.276 0.202
    体质量指数[MP25,P75),kg/m2] 20(19,22) 20(19,22) −0.553 0.580
    供者类型[n(%)] 0.679 0.410
     尸体 24(14) 18(18)
     亲属活体 143(86) 81(82)
    移植术后时间[MP25,P75),d] 9(7,12) 8(7,12) −0.095 0.924
    丙氨酸转氨酶[MP25,P75),IU/L] 15(9,25) 13(9,24) −0.684 0.494
    天冬氨酸转氨酶[MP25,P75),IU/L] 13(11,18) 13(10,17) −0.919 0.358
    碱性磷酸酶[MP25,P75),IU/L] 61(50,79) 62(48,79) −0.341 0.733
    胆红素[MP25,P75),μmol/L] 9(7,11) 9(7,11) −0.655 0.512
    白蛋白[MP25,P75),g/L] 33(31,37) 34(32,37) −1.491 0.136
    白蛋白变化[MP25,P75),g/L] 2.7(1.3,5.2) 2.4(1.1,4.5) −0.458 0.647
    血清肌酐[MP25,P75),μmol/L] 89(73,120) 89(66,112) −1.178 0.239
    白细胞[MP25,P75),×109/L] 9(7,12) 9(7,11) −0.024 0.981
    红细胞比容($\overline x \pm s $) 0.26±0.06 0.26±0.06 −0.507 0.612
    红细胞比容变化[MP25,P75),%] 1.4(0.7,2.3) 2.1(1.0,3.4) −3.177 0.001
    血小板($\overline x \pm s $,×109/L) 212±74 213±55 −0.198 0.844
    CYP3A5*3基因型[n(%)] 4.928 0.085
     GG 73(44) 43(44)
     AG 77(46) 53(54)
     AA 17(10) 3(3)
    G2677T/A基因型[n(%)] 1.825 0.873
     GG 25(15) 18(18)
     AA 5(3) 4(4)
     TT 31(19) 13(13)
     AT 23(14) 13(13)
     GA 26(16) 17(17)
     GT 57(34) 34(34)
    C3435T基因型[n(%)] 4.101 0.129
     CC 61(37) 35(35)
     CT 73(44) 53(54)
     TT 33(20) 11(11)
    C1236T基因型[n(%)] 0.898 0.638
     CC 19(11) 14(14)
     CT 82(49) 51(52)
     TT 66(40) 34(34)
    下载: 导出CSV

    表  2  JPKD预测他克莫司血药浓度准确性的影响因素多因素分析

    Table  2.   Multivariate analysis of factors affecting the accuracy of tacrolimus blood concentration predicted by JPKD

    指标 比值比 95%可信区间 P
    性别 0.627 0.369~1.064 0.084
    红细胞比容变化 1.224 1.071~1.400 0.003
    白蛋白 1.031 0.969~1.097 0.340
    CYP3A5*3 GG 1.000 0.093
    CYP3A5*3 AA 0.251 0.066~0.957 0.043
    CYP3A5*3 AG 1.099 0.638~1.891 0.734
    C3435T CC 1.000 0.149
    C3435T CT 1.326 0.749~2.346 0.333
    C3435T TT 0.599 0.259~1.388 0.232
    下载: 导出CSV
  • [1] 中华医学会器官移植学分会. 器官移植免疫抑制剂临床应用技术规范(2019版)[J]. 器官移植, 2019, 10(3): 213-226. DOI: 10.3969/j.issn.1674-7445.2019.03.001.

    Organ Transplantation Society of Chinese Medical Association. Technical specifications for clinical application of immunosuppressants in organ transplantation (2019)[J]. Organ Transplant, 2019, 10(3): 213-226. DOI: 10.3969/j.issn.1674-7445.2019.03.001.
    [2] WANG XH, SHAO K, AN HM, et al. The pharmacokinetics of tacrolimus in peripheral blood mononuclear cells and limited sampling strategy for estimation of exposure in renal transplant recipients[J]. Eur J Clin Pharmacol, 2022, 78(8): 1261-1272. DOI: 10.1007/s00228-021-03215-9.
    [3] MORAIS MC, SOARES ME, COSTA G, et al. Impact of tacrolimus intra-patient variability in adverse outcomes after organ transplantation[J]. World J Transplant, 2023, 13(5): 254-263. DOI: 10.5500/wjt.v13.i5.254.
    [4] CHEN D, LU H, SUI W, et al. Functional CYP3A variants affecting tacrolimus trough blood concentrations in Chinese renal transplant recipients[J]. Pharmacogenomics J, 2021, 21(3): 376-389. DOI: 10.1038/s41397-021-00216-w.
    [5] 陈文倩, 张雷, 张弋, 等. 实体器官移植他克莫司个体化治疗专家共识[J]. 中国医院用药评价与分析, 2021, 21(12): 1409-1424. DOI: 10.14009/j.issn.1672-2124.2021.12.001.

    CHEN WQ, ZHANG L, ZHANG Y, et al. Expert consensus on individual treatment of tacrolimusin solid organ transplantation[J]. Eval Anal Drug-Use Hosp China, 2021, 21(12): 1409-1424. DOI: 10.14009/j.issn.1672-2124.2021.12.001.
    [6] WOLF U. A drug safety concept (I) to avoid polypharmacy risks in transplantation by individual pharmacotherapy management in therapeutic drug monitoring of immunosuppressants[J]. Pharmaceutics, 2023, 15(9): 2300. DOI: 10.3390/pharmaceutics15092300.
    [7] 广东省药学会. 肾移植患者免疫抑制剂长期管理医药专家共识[J]. 今日药学, 2022, 32(11): 801-816. DOI: 10.12048/j.issn.1674-229X.2022.11.001.

    Guangdong Pharmaceutical Society. Expert consensus on long-term management of immunosuppressants in renal transplant recipients[J]. Pharm Today, 2022, 32(11): 801-816. DOI: 10.12048/j.issn.1674-229X.2022.11.001.
    [8] ETTE EI, WILLIAMS PJ. Population pharmacokinetics I: background, concepts, and models[J]. Ann Pharmacother, 2004, 38(10): 1702-1706. DOI: 10.1345/aph.1D374.
    [9] DUFFULL SB, WRIGHT DF. What do we learn from repeated population analyses?[J]. Br J Clin Pharmacol, 2015, 79(1): 40-47. DOI: 10.1111/bcp.12233.
    [10] GU JQ, GUO YP, JIAO Z, et al. How to handle delayed or missed doses: a population pharmacokinetic perspective[J]. Eur J Drug Metab Pharmacokinet, 2020, 45(2): 163-172. DOI: 10.1007/s13318-019-00598-0.
    [11] TENG F, ZHANG W, WANG W, et al. Population pharmacokinetics of tacrolimus in Chinese adult liver transplant patients[J]. Biopharm Drug Dispos, 2022, 43(2): 76-85. DOI: 10.1002/bdd.2311.
    [12] PASCHIER A, DESTERE A, MONCHAUD C, et al. Tacrolimus population pharmacokinetics in adult heart transplant patients[J]. Br J Clin Pharmacol, 2023, 89(12): 3584-3595. DOI: 10.1111/bcp.15857.
    [13] KAMP J, ZWART TC, MEZIYERH S, et al. Meltdose tacrolimus population pharmacokinetics and limited sampling strategy evaluation in elderly kidney transplant recipients[J]. Pharmaceutics, 2023, 16(1): 17. DOI: 10.3390/pharmaceutics16010017.
    [14] DU Y, SONG W, XIONG X, et al. Population pharmacokinetics and dosage optimisation of tacrolimus coadministration with Wuzhi capsule in adult liver transplant patients[J]. Xenobiotica, 2022, 52(3): 274-283. DOI: 10.1080/00498254.2022.2073851.
    [15] CAI X, SONG H, JIAO Z, et al. Population pharmacokinetics and dosing regimen optimization of tacrolimus in Chinese lung transplant recipients[J]. Eur J Pharm Sci, 2020, 152: 105448. DOI: 10.1016/j.ejps.2020.105448.
    [16] CHENG Y, CHEN J, LIN X, et al. Population pharmacokinetic analysis for model-based therapeutic drug monitoring of tacrolimus in Chinese Han heart transplant patients[J]. Eur J Drug Metab Pharmacokinet, 2023, 48(1): 89-100. DOI: 10.1007/s13318-022-00807-3.
    [17] JING Y, KONG Y, HOU X, et al. Population pharmacokinetic analysis and dosing guidelines for tacrolimus co-administration with Wuzhi capsule in Chinese renal transplant recipients[J]. J Clin Pharm Ther, 2021, 46(4): 1117-1128. DOI: 10.1111/jcpt.13407.
    [18] BRUNET M, VAN GELDER T, ÅSBERG A, et al. Therapeutic drug monitoring of tacrolimus-personalized therapy: second consensus report[J]. Ther Drug Monit, 2019, 41(3): 261-307. DOI: 10.1097/FTD.0000000000 000640.
    [19] 韩璐, 徐方敏, 张晓珊, 等. 个体化给药辅助决策系统Smart Dose、PharmVan与JPKD对万古霉素血药浓度预测能力的评价[J]. 中华危重病急救医学, 2021, 33(3): 263-268. DOI: 10.3760/cma.j.cn121430-20201016- 00674.

    HAN L, XU FM, ZHANG XS, et al. Predictive performance of Smart Dose, PharmVan and JPKD on Vancomycin plasma concentration[J]. Chin Crit Care Med, 2021, 33(3): 263-268. DOI: 10.3760/cma.j.cn121430-20201016-00674.
    [20] 刘雪姣, 周青, 赵宇蕾, 等. 万古霉素个体化给药辅助决策系统在重症患者中的应用[J]. 中国医院药学杂志, 2020, 40(20): 2143-2146,2157. DOI: 10.13286/j.1001-5213.2020.20.10.

    LIU XJ, ZHOU Q, ZHAO YL, et al. Application of vancomycin individualized dosage auxiliary system in ICU patients[J]. Chin J Hosp Pharm, 2020, 40(20): 2143-2146,2157. DOI: 10.13286/j.1001-5213.2020.20.10.
    [21] 何娟, 杨婉花. 基于群体药动学的万古霉素个体化给药模式的建立和临床应用[J]. 中国临床药学杂志, 2015, 24(1): 27-31.

    HE J, YANG WH. Establishment of the individualized drug delivery model of vancomycin for infected patients based on population pharmacokinetics and its clinical application[J]. Chin J Clin Pharm, 2015, 24(1): 27-31.
    [22] 张海波, 吴雨璇, 孔令文, 等. 个体化给药辅助软件应用于万古霉素个体化给药的效果评价[J]. 中国药物滥用防治杂志, 2022, 28(9): 1225-1228. DOI: 10.15900/j.cnki.zylf1995.2022.09.012.

    ZHANG HB, WU YX, KONG LW, et al. Application of personalized drug administration assistant software in vancomycin personalized drug administration[J]. Chin J Drug Abuse Prev Treat, 2022, 28(9): 1225-1228. DOI: 10.15900/j.cnki.zylf1995.2022.09.012.
    [23] 仇晓威. 群体药动学方法调整患者万古霉素使用效果的分析[J]. 医学信息, 2023, 36(22): 97-100. DOI: 10.3969/j.issn.1006-1959.2023.22.021.

    QIU XW. Analysis of the effect of population pharmacokinetic method on adjusting the use of vancomycin in patients[J]. Med Inform, 2023, 36(22): 97-100. DOI: 10.3969/j.issn.1006-1959.2023.22.021.
    [24] 杨浩, 熊雄, 刘长江. 骨科术后患者万古霉素峰谷浓度的影响因素及群体药动学预测比较[J]. 中国医院药学杂志, 2023, 43(24): 2722-2728. DOI: 10.13286/j.1001-5213.2023.24.02.

    YANG H, XIONG X, LIU CJ. Factors influencing peak and trough vancomycin concentrations in postoperative orthopaedic patients and its comparative population pharmacokinetic prediction[J]. Chin Jo Hosp Pharm, 2023, 43(24): 2722-2728. DOI: 10.13286/j.1001-5213.2023.24.02.
    [25] ZHANG HX, SHENG CC, LIU LS, et al. Systematic external evaluation of published population pharmacokinetic models of mycophenolate mofetil in adult kidney transplant recipients co-administered with tacrolimus[J]. Br J Clin Pharmacol, 2019, 85(4): 746-761. DOI: 10.1111/bcp.13850.
    [26] KIRUBAKARAN R, STOCKER SL, HENNIG S, et al. Population pharmacokinetic models of tacrolimus in adult transplant recipients: a systematic review[J]. Clin Pharmacokinet, 2020, 59(11): 1357-1392. DOI: 10.1007/s40262-020-00922-x.
    [27] ASBERG A, FALCK P, UNDSET LH, et al. Computer-assisted cyclosporine dosing performs better than traditional dosing in renal transplant recipients: results of a pilot study[J]. Ther Drug Monit, 2010, 32(2): 152-158. DOI: 10.1097/FTD.0b013e3181d3f822.
    [28] FAELENS R, LUYCKX N, KUYPERS D, et al. Predicting model-informed precision dosing: a test-case in tacrolimus dose adaptation for kidney transplant recipients[J]. CPT Pharmacometrics Syst Pharmacol, 2022, 11(3): 348-361. DOI: 10.1002/psp4.12758.
    [29] 刘晓芹, 焦正, 高玉成, 等. 个体化给药辅助决策系统研究与应用进展[J]. 中国药学杂志, 2019, 54(1): 1-8. DOI: 10.11669/cpj.2019.01.001.

    LIU XQ, QIAO Z, GAO YC, et al. Progress in development and application of decision-making systems for individualized dosing[J]. Chin Pharm J, 2019, 54(1): 1-8. DOI: 10.11669/cpj.2019.01.001.
    [30] 陆晓玲, 王雨萍, 邵琨, 等. CYP3A5、ABCB1基因多态性对中国肾移植患者服用他克莫司剂量和血药浓度的影响[J]. 药学与临床研究, 2023, 31(6): 481-485.

    LU XL, WANG YP, SHAO K, et al. Effects of CYP3A5 and ABCB1 gene polymorphisms on dosages and blood concentrations of tacrolimus in chinese kidney transplant patients[J]. Pharm Clin Res, 2023, 31(6): 481-485.
    [31] CHAUHAN PM, HEMANI RJ, SOLANKI ND, et al. A systematic review and meta-analysis recite the efficacy of Tacrolimus treatment in renal transplant patients in association with genetic variants of CYP3A5 gene[J]. Am J Clin Exp Urol, 2023, 11(4): 275-292.
    [32] LU H, JIANG H, YANG S, et al. Trans-eQTLs of the CYP3A4 and CYP3A5 associated with tacrolimus trough blood concentration in Chinese renal transplant patients[J]. Biomed Pharmacother, 2022, 145: 112407. DOI: 10.1016/j.biopha.2021.112407.
    [33] HANNACHI I, CHADLI Z, KERKENI E, et al. Influence of CYP3A polymorphisms on tacrolimus pharmacokinetics in kidney transplant recipients[J]. Pharmacogenomics J, 2021, 21(1): 69-77. DOI: 10.1038/s41397-020-00179-4.
    [34] YU M, LIU M, ZHANG W, et al. Pharmacokinetics, pharmacodynamics and pharmacogenetics of tacrolimus in kidney transplantation[J]. Curr Drug Metab, 2018, 19(6): 513-522. DOI: 10.2174/138920021966618012915 1948.
    [35] CAI XJ, LI RD, LI JH, et al. Prospective population pharmacokinetic study of tacrolimus in adult recipients early after liver transplantation: a comparison of Michaelis-Menten and theory-based pharmacokinetic models[J]. Front Pharmacol, 2022, 13: 1031969. DOI: 10.3389/fphar.2022.1031969.
    [36] FRANKEN LG, FRANCKE MI, ANDREWS LM, et al. A population pharmacokinetic model of whole-blood and intracellular tacrolimus in kidney transplant recipients[J]. Eur J Drug Metab Pharmacokinet, 2022, 47(4): 523-535. DOI: 10.1007/s13318-022-00767-8.
    [37] KHAMLEK K, KOMENKUL V, SRIBOONRUANG T, et al. Population pharmacokinetic models of tacrolimus in paediatric solid organ transplant recipients: a systematic review[J]. Br J Clin Pharmacol, 2024, 90(2): 406-426. DOI: 10.1111/bcp.15909.
    [38] ZAHIR H, MCLACHLAN AJ, NELSON A, et al. Population pharmacokinetic estimation of tacrolimus apparent clearance in adult liver transplant recipients[J]. Ther Drug Monit, 2005, 27(4): 422-430. DOI: 10.1097/01.ftd.0000170029.36573.a0.
  • 加载中
图(1) / 表(2)
计量
  • 文章访问数:  8
  • HTML全文浏览量:  3
  • PDF下载量:  0
  • 被引次数: 0
出版历程
  • 收稿日期:  2024-02-20
  • 网络出版日期:  2024-04-28

目录

    /

    返回文章
    返回