Estimation model for the exposure of mycophenolic acid in early renal transplant recipients

ZHANG Hanjuan; DING Jianqiang; HAN Wenchao; CHEN Yongyan; WANG Gaobiao; DING Rui; YUAN Dongdong

doi:10.6039/j.issn.1001-0408.2023.20.15

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Estimation model for the exposure of mycophenolic acid in early renal transplant recipients

更新时间：2023-10-25

- Estimation model for the exposure of mycophenolic acid in early renal transplant recipients
- ZHONGGUO YAOFANG Vol. 34, Issue 20, Pages: 2530-2534(2023)
- 作者机构：
  
  1.郑州市第七人民医院药学部，郑州　450016
  2.武警河南总队医院药学部，郑州　450052
- 作者简介：
- 基金信息：
- DOI：10.6039/j.issn.1001-0408.2023.20.15
  CLC： R969
- Published：30 October 2023，
  
  Received：13 March 2023，
  
  Revised：25 September 2023，
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张寒娟,丁建强,韩文超等.肾移植受者早期霉酚酸暴露量估算模型研究 ^Δ[J].中国药房,2023,34(20):2530-2534.

ZHANG Hanjuan,DING Jianqiang,HAN Wenchao,et al.Estimation model for the exposure of mycophenolic acid in early renal transplant recipients[J].ZHONGGUO YAOFANG,2023,34(20):2530-2534.
张寒娟,丁建强,韩文超等.肾移植受者早期霉酚酸暴露量估算模型研究 ^Δ[J].中国药房,2023,34(20):2530-2534. DOI： 10.6039/j.issn.1001-0408.2023.20.15.

ZHANG Hanjuan,DING Jianqiang,HAN Wenchao,et al.Estimation model for the exposure of mycophenolic acid in early renal transplant recipients[J].ZHONGGUO YAOFANG,2023,34(20):2530-2534. DOI： 10.6039/j.issn.1001-0408.2023.20.15.

摘要

目的

建立肾移植早期受者体内霉酚酸（MPA）暴露量[以12 h内血药浓度-时间曲线下面积（AUC

0－12 h

）计]的估算模型。

方法

选择20例接受吗替麦考酚酯（MMF）+他克莫司+甲泼尼龙三联免疫抑制治疗的肾移植受者，分别于术后第15天口服吗替麦考酚酯分散片（750 mg，q12 h）前及服药后0.5、1.0、1.5、2.0、3.0、4.0、6.0、8.0、12.0 h采集血样，测定MPA血药浓度，计算MPA的药动学参数；采用多元线性逐步回归分析法，拟合估算受者人群体内MPA-AUC

0－12 h

的有限采样法简化计算公式，并采用Bland-Altman方法评价该公式与经典药动学方法之间的一致性。

结果

20例受者MPA的给药前血药浓度（

）为（1.53±0.84）μg/mL，药峰浓度（

max

）为（12.07±5.97）μg/mL，半衰期（

1/2

）为（5.41±3.67）h，药峰时间（

max

）为（1.58±0.75）h，fAUC

0－12 h

（按经典药动学方法计算出的AUC

0－12 h

）为（33.95±13.40）μg·h/mL。使用“4.0、8.0、12.0 h”三点采样估算MPA-AUC

0－12 h

的简化计算公式为AUC

0－12 h

＝12.058+2.819

4.0

+7.045

8.0

+3.879

12.0

（

＝0.934），预测值与fAUC

0－12 h

有很好的相关性及一致性，95.0%的预测值在

±1.96SD（标准差）范围内。

结论

成功建立了肾移植受者早期MPA暴露量估算模型，且该模型有较好的预测精度，并具有采样点少的优势。

Abstract

OBJECTIVE

To establish the estimation model for the exposure of mycophenolic acid （MPA） in early renal transplant recipients [calculated by the area under the plasma concentration-time curve with 12 h （AUC

0－12 h

）].

METHODS

Twenty kidney transplant recipients， who received triple immunosuppressive therapy of mycophenolate mofetil （MMF）+tacrolimus+methylprednisolone， were selected and given MMF dispersible tablets （750 mg， q12 h） on the 15th day after the operation； the blood samples were collected from the patients before and 0.5， 1.0， 1.5， 2.0， 3.0， 4.0， 6.0， 8.0， 12.0 hours after the administration， respectively. The blood concentration of MPA was determined， and the pharmacokinetic parameters of MPA were calculated. The multivariate linear stepwise regression analysis method was used to fit an estimation formula for the finite sampling method suitable for MPA-AUC

0－12 h

of the recipients. Bland-Altman analysis was used to evaluate the agreement between the estimation formula and the classical pharmacokinetic method.

RESULTS

The main pharmacokinetic parameters of MPA in 20 renal transplant recipients：

was （1.53±0.84） μg/mL，

max

was （12.07±5.97） μg/mL，

1/2

was （5.41±3.67） h，

max

was （1.58±0.75） h， and the average AUC

0－12 h

calculated by the classical pharmacokinetic method was （33.95±13.40） μg·h/mL. MPA-AUC

0－12 h

was estimated with sampling points of “4.0， 8.0， 12.0 h”； the simplified calculation formula was AUC

0－12 h

＝12.058+2.819

4.0

+7.045

8.0

+3.879

12.0

（

＝0.934）. The predicted value had a good correlation and consistency with the measured value， and 95.0% of predicted values did not exceed the

±1.96SD （standard deviation） range.

CONCLUSIONS

The estimation model is established successfully for the exposure of MPA in early renal transplant recipients； the model has better prediction accuracy and fewer sampling points.

关键词

霉酚酸暴露量肾移植药动学有限采样法预测模型

Keywords

exposurerenal transplantationpharmacokineticslimited sampling strategyestimation model

references

STAATZ C E，TETT S E. Clinical pharmacokinetics and pharmacodynamics of mycophenolate in solid organ transplant recipients[J]. Clin Pharmacokinet，2007，46（1）：13-58.

曾维胜，李珍，宋秘，等. 性别对肾移植受体霉酚酸血药浓度影响的临床分析[J]. 器官移植，2018，9（5）：385-389.

ZENG W S，LI Z，SONG M，et al. Clinical analysis of the influence of gender on blood concentration of mycophenolic acid in recipients undergoing renal transplantation[J]. Organ Transplant，2018，9（5）：385-389.

CIANCIO G，MILLER J，GONWA T A. Review of major clinical trials with mycophenolate mofetil in renal transplantation[J]. Transplantation，2005，80（2 Suppl）：S191-S200.

KUYPERS D R J，MEUR Y L，CANTAROVICH M，et al. Consensus report on therapeutic drug monitoring of mycophenolic acid in solid organ transplantation[J]. Clin J Am Soc Nephrol，2010，5（2）：341-358.

RASK C，ALBERTIONI F，BENTZEN S M，et al. Clinical and pharmacokinetic risk factors for high-dose methotrexate-induced toxicity in children with acute lymphoblastic leukemia：a logistic regression analysis[J]. Acta Oncol，1998，37（3）：277-284.

ANDREWS L M，RIVA N，DE WINTER B C，et al. Do-sing algorithms for initiation of immunosuppressive drugs in solid organ transplant recipients[J]. Expert Opin Drug Metab Toxicol，2015，11（6）：921-936.

谢何琳，吴雪梅，庄波阳，等. 有限采样法监测造血干细胞移植患者的白消安血药浓度[J]. 中国药学杂志，2015，50（16）：1424-1429.

XIE H L，WU X M，ZHUANG B Y，et al. Limited sampling strategies for clinical plasma concentration monito-ring of busulfan in hematopoietic stem cell transplantation patients[J]. Chin Pharm J，2015，50（16）：1424-1429.

FILLER G. Abbreviated mycophenolic acid AUC from c0，c1，c2，and c4 is preferable in children after renal transplantation on mycophenolate mofetil and tacrolimus therapy[J]. Transpl Int，2004，17（3）：120-125.

杨顺良，高霞，王庆华，等. 有限采样策略估算肾移植受者霉酚酸钠药-时曲线下面积方法的建立[J]. 中华医学杂志，2013，93（48）：3841-3846.

YANG S L，GAO X，WANG Q H，et al. Use of limited sampling strategy for estimating area under concentration-time curve of mycophenolate sodium in renal allograft recipients[J]. Natl Med J China，2013，93（48）：3841-3846.

叶丽卡，谢志红，王若伦，等. 有限采样法估算霉酚酸药-时曲线下面积[J]. 中国药学杂志，2009，44（8）：611-614.

YE L K，XIE Z H，WANG R L，et al. Limited sampling strategy for estimating the area under concentration-time curve of mycophenolic acid[J]. Chin Pharm J，2009，44（8）：611-614.

杨玉玲，孙迪迪，张寒娟，等. 全自动二维高效液相色谱测定霉酚酸血药浓度的研究[J]. 中国医院药学杂志，2020，40（19）：2051-2054.

YANG Y L，SUN D D，ZHANG H J，et al. Measurement of mycophenolic acid in blood by two-dimensional liquid chromatography[J]. Chin J Hosp Pharm，2020，40（19）：2051-2054.

付美子，林炳清. 临床测量中定量数据Bland-Altman一致性评价[J]. 广西师范大学学报（自然科学版），2022，40（1）：125-138.

FU M Z，LIN B Q. Bland-Altman method for assessing agreement of quantitative data in clinical measurement[J]. J Guangxi Norm Univ Nat Sci Ed，2022，40（1）：125-138.

李纳，朱振峰，丰贵文，等. 有限采样法估算麦考酚钠药-时曲线下面积及其药动学[J]. 医药导报，2016，35（11）：1177-1180.

LI N，ZHU Z F，FENG G W，et al. Limited sampling stra-tegy for the estimation of mycophenolate sodium area under concentration-time curve and pharmacokinetic study[J]. Her Med，2016，35（11）：1177-1180.

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