中国 COVID-19 重症患者中尼马瑞韦/利托那韦的群体药代动力学及用药建议:一项双中心回顾性研究。

IF 3.6 3区 医学 Q2 PHARMACOLOGY & PHARMACY
Junjun Xu, Jinmeng Li, Meng Chen, Huifang Jiang, Xudong Fan, Yangmin Hu, Haili Shan, Mingdong Yang, Yichao Xu, Yuying Lang, Haibin Dai, Xinjun Cai
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引用次数: 0

摘要

研究背景本研究旨在建立中国2019年冠状病毒病(COVID-19)感染重症患者中尼马瑞韦/利托那韦的群体药代动力学(PPK)模型,探讨影响尼马瑞韦/利托那韦药代动力学(PK)的因素:方法:共收集了152名患者的285份血清样本和临床数据。采用非线性混合效应模型(NONMEM)方法分析了那瑞瑞韦/利托那韦的药代动力学(PK)模型。通过蒙特卡洛模拟确定了不同肾功能患者的最佳给药方案:结果:nirmatrelvir 的表观清除率(CL/F)和表观分布容积(V/F)的人群典型值分别为 2.26 L/h 和 15.3 L。值得注意的是,肌酐清除率(CrCL)对尼尔马特韦的 PK 变化有显著影响。蒙特卡洛模拟显示,与肾功能正常的患者相比,轻度至中度肾功能受损的患者在服用标准剂量的尼尔马特韦时,其曲线下面积(AUC)会增加 22.0-59.9%。严重肾功能损害患者服用150毫克 q12小时的尼尔马特雷韦后,其AUC与肾功能正常患者服用300毫克 q12小时的尼尔马特雷韦后的AUC相似:PPK建模和模拟为尼马瑞韦/利托那韦在中国重症患者中的临床合理应用提供了参考。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Population pharmacokinetics of nirmatrelvir/ritonavir in critically ill Chinese COVID-19 patients and recommendations for medication use: a two-center retrospective study.

Background: This study aimed to establish population pharmacokinetics (PPK) models of nirmatrelvir/ritonavir in critically ill Chinese patients with the coronavirus disease 2019 (COVID-19) infection, explore factors affecting the pharmacokinetics (PK) of nirmatrelvir/ritonavir.

Methods: A total of 285 serum samples and clinical data were collected from 152 patients. The PPK models of nirmatrelvir/ritonavir were analyzed using nonlinear mixed-effect modeling (NONMEM) approach. The optimal dosing regimen for patients with different renal function was determined using Monte Carlo simulations.

Results: The population typical values of apparent clearance (CL/F) and apparent volume of distribution (V/F) of nirmatrelvir were 2.26 L/h and 15.3 L, respectively. Notably, creatinine clearance (CrCL) significantly influenced the PK variation of nirmatrelvir. Monte Carlo simulations suggested that patients with mild-to-moderate renal impairment experienced a 22.0-59.9% increase in the area under the curve (AUC) when they were administered a standard dose of nirmatrelvir compared to those with normal renal function. The AUC in patients with severe renal impairment after administration of 150 mg q12h nirmatrelvir was similar to that in patients with normal renal function after administration of 300 mg q12h nirmatrelvir.

Conclusions: PPK modeling and simulation provided a reference for the rational clinical application of nirmatrelvir/ritonavir in critically ill Chinese patients.

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来源期刊
Expert Review of Clinical Pharmacology
Expert Review of Clinical Pharmacology PHARMACOLOGY & PHARMACY-
CiteScore
7.30
自引率
2.30%
发文量
127
期刊介绍: Advances in drug development technologies are yielding innovative new therapies, from potentially lifesaving medicines to lifestyle products. In recent years, however, the cost of developing new drugs has soared, and concerns over drug resistance and pharmacoeconomics have come to the fore. Adverse reactions experienced at the clinical trial level serve as a constant reminder of the importance of rigorous safety and toxicity testing. Furthermore the advent of pharmacogenomics and ‘individualized’ approaches to therapy will demand a fresh approach to drug evaluation and healthcare delivery. Clinical Pharmacology provides an essential role in integrating the expertise of all of the specialists and players who are active in meeting such challenges in modern biomedical practice.
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