在稳定的移植患者中,贝叶斯对塔克罗利斯暴露的优化
Thomas D Nguyen1,2, Nicholas M Smith1,2, Kris Attwood3
1School of Pharmacy & Pharmaceutical Sciences, University at Buffalo, Buffalo, New York, USA.
Pharmacotherapy
|July 15, 2023
概括
使用稀疏采样对塔克罗利木斯AUC0-12的最大后期贝叶斯式 (MAP-Bayesian) 估计与移植接受者 (KTRs) 的非分区分析 (NCA) 相似. 这种方法可以改善KTRs的治疗药物监测 (TDM).
科学领域:
- 药理动力学和药理动力学
- 移植医学 移植医学 移植医学
- 临床药理学 临床药理学
背景情况:
- 塔克罗利马斯是移植接受者 (KTRs) 的重要免疫抑制剂.
- 精确监测塔克罗利斯暴露,特别是度-时间曲线下的区域 (AUC0-12),对于优化疗效和最大限度地降低毒性至关重要.
- 传统的非分组分析 (NCA) 需要进行密集的血液采样,这对患者来说可能是负担.
研究的目的:
- 为了比较NCA使用密集采样确定的tacrolimus AUC0-12与从稀疏采样获得的最大后期贝叶斯式 (MAP-Bayesian) 估计.
- 评估强大的 (9个样本/受试者) 和稀疏的 (2个样本/受试者) MAP-贝叶斯方法在稳定的KTR中估计塔克罗利斯暴露的实用性.
- 评估MAP-贝叶斯估计的潜力,以有限的抽样来加强KTRs的治疗药物监测 (TDM).
主要方法:
- 在67个稳定的KTR中进行了一项开放标签,前性,单中心的药理动力学研究.
- 使用密集的连续采样 (每人9个样本) 来确定NCA塔克罗利斯稳定状态AUC0-12.
- 用先进剂量解决方案 (AdDS) 和ADAPT5软件使用强大和稀疏的采样策略获得了AUC0-12的MAP-贝叶斯估计.
- 评估方法之间的一致性是使用配对的t测试,类内相关系数 (ICC) 和布兰德·奥尔特曼分析.
- 用一个由15个KTR组成的验证组来证实这些发现.
主要成果:
- 在训练组 (n=67) 中,NCA-AUC0-12为123.8±33.6μg·h/L. 马普-贝叶斯估计显示出高度一致:强大的AUC0-12为124.7±33.3μg·h/L (ICC=0.96) 和最佳的2个样本的Sparse-AUC0-12为119.7±32.7μg·h/L.
- 最优的稀疏采样策略 (剂前和剂后1小时) 与NCA (ICC=0.93) 显示出强烈的相关性.
- 在验证组 (n=15) 中,MAP-贝叶斯估计值 (Robust-AUC0-12: 85.1 ± 33.8 μg·h/L; Sparse-AUC0-12: 86.7 ± 33.9 μg·h/L) 与NCA-AUC0-12 (88.4 ± 33.1 μg·h/L) 相当,ICC值分别为0.93和0.91.
结论:
- 使用稀疏,两种样本采样对患者特异性塔克罗利斯AUC0-12的MAP-贝叶斯估计是密集采样NCA的可靠替代方案.
- 这种方法证明了与NCA的良好协议,表明其有潜力提高TACROLIMUS TDM在稳定的KTR中的效率和实用性.
- 实施稀疏的MAP-贝叶斯方法可以促进更频繁,更方便的监测,从而改善患者的治疗结果.
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