开发和验证一个人群的药理动力学模型,以指导肺移植后的外科手术期间的塔克罗利斯剂量
medRxiv : the preprint server for health sciences
|July 10, 2023
概括
肺移植后的塔克罗利马斯暴露在早期康复过程中变化很大. 手术后的一天是影响塔克罗利斯清除的关键因素,这凸显了移植患者需要仔细监测的必要性.
科学领域:
- 药理动力学 药理动力学
- 移植医学 移植医学
- 免疫抑制疗法是一种免疫抑制疗法.
背景情况:
- 塔克罗利斯是肺移植后的标准免疫抑制剂.
- 早期术后塔克罗利斯暴露的变化与不良结果有关.
- 有限的研究存在于早期的肺移植后塔克罗利斯的药理动力学.
研究的目的:
- 在肺移植后早期接受者中开发和验证塔克罗利斯的药理动力学模型.
- 确定影响高风险早期术后期中塔克罗利莫斯暴露的关键共变量.
主要方法:
- 对270名肺移植接受者的回顾性药理动力学研究.
- 使用NONMEM的模型开发,在114名患者的单独队列中得到验证.
- 共变量分析包括单变量和多变量阶段性选择.
主要成果:
- 开发了一个单间模型,确定术后的一天,血红素,移植类型,CYP3A5基因型,体重和CYP抑制剂药物作为显著的共同变量.
- 手术后的一天是最强的预测因素,在14天内,塔克罗利斯清除率增加了三倍以上.
- 最终模型在验证队列中表现良好 (平均PE为36.4%).
结论:
- 手术后的一天是肺移植早期阶段塔克罗利斯暴露的主要决定因素.
- 需要进行更多的多中心研究,采用密集的样本,以充分阐明影响该群体中塔克罗利斯药理动学的因素.
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