用有限采样模型估算造血干细胞移植受者体内霉酚酸的曲线下面积。

IF 1.7 4区 医学 Q3 PHARMACOLOGY & PHARMACY
Liangmo Lin, Mianhui Hong, Xiangjun Fu
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引用次数: 0

摘要

在实体器官移植受者中,霉酚酸(MPA)的曲线下面积(AUC)与发生排斥反应的可能性之间的关系已得到证实。在造血干细胞移植(HSCT)中,MPA的AUC也与移植物抗宿主疾病有关。本研究旨在开发一种简化方法,用于估算接受异基因造血干细胞移植(allo-HSCT)的中国患者的MPA AUC0-12。研究对22名口服霉酚酸酯的患者进行了强化采样。测量了血浆中总 MPA 的浓度,并通过回归分析利用这 22 名患者的数据建立了预测 AUC0-12 的模型。在另外 20 名患者中评估了最合适模型的准确性。没有任何一种 MPA 浓度与 AUC0-12 有很强的相关性(r2 0-12 (r2 > 0.87))。操作上最可行的模型具有良好的预测性能,平均绝对百分比误差 (APE%) 为 0-12。利用 12 小时内 4 次口服浓度(服药后 0、0.5、1 和 4 小时)建立的模型可有效估算 MPA AUC0-12,结果精确且偏差最小。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
A limited sampling model to estimate the area under the curve of mycophenolic acid in hematopoietic stem cell transplantation recipients.

Relationship between the areas under the curve (AUC) of mycophenolic acid (MPA) and the likelihood of rejection is well-established in solid organ transplantation recipients. In hematopoietic stem cell transplantation (HSCT), MPA AUC is also linked to graft versus host disease. This study aimed to develop a simplified method to estimate MPA AUC0-12 in Chinese patients undergoing allogeneic HSCT (allo-HSCT). Intensive sampling was conducted in 22 patients who were orally administered mycophenolate mofetil. Plasma concentrations of total MPA were measured, and a model predicting AUC0-12 using data from these 22 patients was constructed through regression analysis. The accuracy of the most suitable model was assessed in an additional 20 patients. None of the individual MPA concentrations showed a strong correlation with AUC0-12 (r2 < 0.7). Models utilizing 4 or more concentrations were found to effectively estimate MPA AUC0-12 (r2 > 0.87). The most operationally feasible model demonstrated good predictive performance with a mean absolute percentage error (APE%) < 20%. Single MPA concentrations showed poor correlation with MPA AUC0-12. A model utilizing 4 oral concentrations (0, 0.5, 1, and 4 h postdose) over a 12-h period could effectively estimate MPA AUC0-12 with precise results and minimal bias.

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来源期刊
CiteScore
3.60
自引率
0.00%
发文量
35
审稿时长
6-12 weeks
期刊介绍: Biopharmaceutics & Drug Dispositionpublishes original review articles, short communications, and reports in biopharmaceutics, drug disposition, pharmacokinetics and pharmacodynamics, especially those that have a direct relation to the drug discovery/development and the therapeutic use of drugs. These includes: - animal and human pharmacological studies that focus on therapeutic response. pharmacodynamics, and toxicity related to plasma and tissue concentrations of drugs and their metabolites, - in vitro and in vivo drug absorption, distribution, metabolism, transport, and excretion studies that facilitate investigations related to the use of drugs in man - studies on membrane transport and enzymes, including their regulation and the impact of pharmacogenomics on drug absorption and disposition, - simulation and modeling in drug discovery and development - theoretical treatises - includes themed issues and reviews and exclude manuscripts on - bioavailability studies reporting only on simple PK parameters such as Cmax, tmax and t1/2 without mechanistic interpretation - analytical methods
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