Real-world Plasma Exposure of Nirmatrelvir/Ritonavir in Chinese Hospitalized Patients With COVID-19: A Multicenter Retrospective Study.

IF 2.8 4区医学 Q2 MEDICAL LABORATORY TECHNOLOGY

Therapeutic Drug Monitoring Pub Date : 2025-01-30 DOI:10.1097/FTD.0000000000001305

Zhiyuan Ma, Mengru Bai, Shuying Shen, Junshan Zhou, Rong Dong, Jiangjun Zhang, Yayun Weng, Li Li, Yongchen Li, Dan Liu, Wei Yan, Nengming Lin, Jianmei Xia

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引用次数: 0

Abstract

Background: Nirmatrelvir/ritonavir is licensed for the treatment of mild-to-moderate coronavirus disease (COVID-19) in patients at an increased risk of progression to severe disease. However, data on the real-world plasma exposure to nirmatrelvir/ritonavir remain limited, particularly in Chinese patients. This study aimed to assess the nirmatrelvir/ritonavir trough concentration (Ctrough) and identify its critical factors in hospitalized Chinese patients treated with nirmatrelvir/ritonavir 300 mg/100 mg twice daily over a 5-day course.

Methods: A high-performance liquid chromatography-tandem mass spectrometry assay was developed and validated to measure the nirmatrelvir/ritonavir Ctrough. Correlation analyses were performed to identify the variables influencing nirmatrelvir/ritonavir Ctrough.

Results: Among the 110 patients, 100% had plasma concentrations above the antiviral in vitro 90% effective concentration. The median Ctrough of nirmatrelvir was 4.55 mcg/mL (15.6× 90% effective concentration), ranging from 0.65 to 12.44 mcg/mL. Nirmatrelvir Ctrough in normal and mild renal impairment cohorts were comparable (4.09 ± 1.97 mcg/mL and 4.57 ± 2.21 mcg/mL) but significantly increased in the moderate renal impairment cohort (6.41 ± 2.31 mcg/mL). Sex, age, and obesity were not significantly associated with nirmatrelvir exposure.

Conclusions: Nirmatrelvir Ctrough was high in Chinese patients with COVID-19, and therapeutic drug monitoring should not be routinely recommended, except in patients with renal impairment.

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中国住院COVID-19患者尼马特瑞韦/利托那韦的真实血浆暴露：一项多中心回顾性研究

背景：Nirmatrelvir/ritonavir被批准用于治疗进展为严重疾病风险增加的轻至中度冠状病毒病（COVID-19）患者。然而，关于实际血浆暴露于尼马特利韦/利托那韦的数据仍然有限，特别是在中国患者中。本研究旨在评估尼马特利韦/利托那韦的谷浓度（Ctrough），并确定其关键因素在住院的中国患者接受尼马特利韦/利托那韦300 mg/100 mg，每天两次，5天疗程。方法：建立高效液相色谱-串联质谱法测定尼马特利韦/利托那韦的含量。通过相关分析确定影响尼马特韦/利托那韦的变量。结果：110例患者血药浓度均高于抗病毒药物体外90%有效浓度。nirmatrelvir的中位剂量为4.55 mcg/mL （15.6× 90%有效浓度），范围为0.65 ~ 12.44 mcg/mL。尼马特瑞韦在正常和轻度肾损害队列中的剂量相当（分别为4.09±1.97 mcg/mL和4.57±2.21 mcg/mL），但在中度肾损害队列中的剂量显著增加（6.41±2.31 mcg/mL）。性别、年龄和肥胖与尼马特瑞韦暴露无显著相关。结论：中国新冠肺炎患者尼马特瑞韦剂量较高，除肾功能损害患者外，不应常规推荐使用治疗性药物监测。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Therapeutic Drug Monitoring 医学-毒理学

CiteScore

5.00

自引率

8.00%

发文量

213

审稿时长

4-8 weeks

期刊介绍： Therapeutic Drug Monitoring is a peer-reviewed, multidisciplinary journal directed to an audience of pharmacologists, clinical chemists, laboratorians, pharmacists, drug researchers and toxicologists. It fosters the exchange of knowledge among the various disciplines–clinical pharmacology, pathology, toxicology, analytical chemistry–that share a common interest in Therapeutic Drug Monitoring. The journal presents studies detailing the various factors that affect the rate and extent drugs are absorbed, metabolized, and excreted. Regular features include review articles on specific classes of drugs, original articles, case reports, technical notes, and continuing education articles.