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不同霉酚酸剂型在儿童肾移植不同年龄段的暴露差异

张杰, 成富民, 朱昆仑, 等. 不同霉酚酸剂型在儿童肾移植不同年龄段的暴露差异[J]. 器官移植, 2022, 13(3): 356-362. doi: 10.3969/j.issn.1674-7445.2022.03.012
引用本文: 张杰, 成富民, 朱昆仑, 等. 不同霉酚酸剂型在儿童肾移植不同年龄段的暴露差异[J]. 器官移植, 2022, 13(3): 356-362. doi: 10.3969/j.issn.1674-7445.2022.03.012
Zhang Jie, Cheng Fumin, Zhu Kunlun, et al. Exposure difference of various dosage forms of mycophenolic acid in different age groups of pediatric kidney transplantation[J]. ORGAN TRANSPLANTATION, 2022, 13(3): 356-362. doi: 10.3969/j.issn.1674-7445.2022.03.012
Citation: Zhang Jie, Cheng Fumin, Zhu Kunlun, et al. Exposure difference of various dosage forms of mycophenolic acid in different age groups of pediatric kidney transplantation[J]. ORGAN TRANSPLANTATION, 2022, 13(3): 356-362. doi: 10.3969/j.issn.1674-7445.2022.03.012

不同霉酚酸剂型在儿童肾移植不同年龄段的暴露差异

doi: 10.3969/j.issn.1674-7445.2022.03.012
基金项目: 

河南省药物临床试验重点项目 TA2021-565

详细信息
    作者简介:
    通讯作者:

    丰贵文,男,1963年生,博士,主任医师,研究方向为肾移植,Email:fengguiwen@zzu.edu.cn

  • 中图分类号: R617, R726.9

Exposure difference of various dosage forms of mycophenolic acid in different age groups of pediatric kidney transplantation

More Information
  • 摘要:   目的  探讨儿童肾移植术后服用不同霉酚酸(MPA)制剂在≤12岁与 > 12岁年龄段的暴露差异。  方法  回顾性分析73例接受心脏死亡器官捐献(DCD)儿童肾移植受者的临床资料,术后免疫抑制方案均为MPA+他克莫司+糖皮质激素,按照MPA剂型分为A组(37例,服用吗替麦考酚酯胶囊)、B组(28例,服用麦考酚钠肠溶片)和C组(8例,服用吗替麦考酚酯分散片)。并根据移植时患者年龄分为≤12岁年龄段和 > 12岁年龄段。计算不同药物剂型每日给药剂量,采用酶放大免疫法检测MPA血药浓度(C)与曲线下面积(AUC),比较各组不同时间点和两个年龄段的MPA血药浓度,分析受者术后肾功能恢复情况及并发症发生情况。  结果  A、B、C组给药剂量和各时间点血药浓度比较,差异均无统计学意义(均为P > 0.05)。≤12岁年龄段MPA-C4 h、AUC均高于 > 12岁年龄段,差异均有统计学意义(均为P < 0.05)。B组≤12岁年龄段MPA-C4 h高于 > 12岁年龄段,差异有统计学意义(P=0.016)。B组≤12岁年龄段MPA-C4 h较A组和C组高,但差异无统计学意义(P=0.080)。3组急性排斥反应和感染发生率差异均无统计学意义(均为P > 0.05)。  结论  不同年龄段儿童肾移植术后服用不同MPA制剂有不同的暴露率,≤12岁儿童肾移植受者暴露率较 > 12岁儿童有升高的趋势,但主要表现在服用麦考酚钠肠溶片的受者中。因此,监测MPA的暴露水平是必要的,对调整不同剂型药物用量具有较大的指导意义。

     

  • 表  1  3组MPA-AUC及各时间点MPA血药浓度比较

    Table  1.   Comparison of MPA-AUC and MPA blood concentration at each time point in three groups [M(P25, P75)]

    指标 A组(n=37) B组(n=28) C组(n=8) P
    AUC(μg·h/mL) 48.11(32.64,62.86) 49.78(43.52,70.68) 47.02(37.17,61.03) 0.412
    C0 h(μg/mL) 2.05(0.89,4.05) 2.48(1.26,3.38) 0.854
    C1 h(μg/mL) 8.96(4.35,14.01) 4.86(2.27,9.58) 7.34(2.85,9.58) 0.062
    C1.5 h(μg/mL) 6.02(3.29,20.02)
    C2 h(μg/mL) 5.59(4.02,8.99) 9.54(4.80,19.50) 4.53(3.67,8.28) 0.108
    C4 h(μg/mL) 2.75(2.11,4.81) 3.15(2.44,6.11) 2.75(2.07,3.62) 0.492
    注:①−为无数据。
    下载: 导出CSV

    表  2  各组不同年龄段各药物剂型MPA血药浓度比较

    Table  2.   Comparison of MPA blood concentrations of different dosage forms among each group at different age [M(P25, P75)]

    组别 C2 h(μg/mL) C4 h(μg/mL) AUC(μg·h/mL)
    ≤12岁 > 12岁 ≤12岁 > 12岁 ≤12岁 > 12岁
    A组 6.20(3.34,13.91) 5.59(4.70,8.41) 3.49(2.27,4.58) 2.60(2.08,5.04) 53.20(34.91,73.12) 41.29(32.20,58.29)
    B组 10.02(5.93,19.16) 9.06(2.82,20.00) 5.78(2.71,8.20) 2.65(1.85,3.79) 55.04(46.86,98.57) 47.55(40.11,49.95)
    C组 4.05(3.23,7.59) 7.48(4.73,8.54) 2.89(1.93,5.06) 2.61(2.04,3.68) 50.42(35.49,57.63) 43.62(37.06,68.43)
    P 0.116 0.646 0.080 0.916 0.129 0.738
    下载: 导出CSV
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  • 收稿日期:  2022-02-01
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