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影响新冠病毒感染者中奈玛特韦/利托那韦浓度的因素

Factors influencing Nirmatrelvir/Ritonavir concentration in patients with COVID-19.

作者信息

Xu Ping, Zhang Lijun, Wu Qingguo

机构信息

Department of Respiratory and Critical Care Medicine, Shanghai Public Health Clinical Center, Shanghai, 201508, People's Republic of China.

Department of Clinical Research, Shanghai Public Health Clinical Center, Shanghai, 201508, People's Republic of China.

出版信息

BMC Infect Dis. 2024 Dec 18;24(1):1425. doi: 10.1186/s12879-024-10291-6.

Abstract

BACKGROUND

In the filed of antiviral therapy, effective therapeutic concentration is beneficial to shorten the recovery time of patients and reduce the transmission rate.The aim of this study is to retrospectively analyze the factors that lead to the drug concentration of Nirmatrelvir /Ritonavir (NMV/RTV) not reaching the standard.

METHODS

In this study, the NMV/RTV drug concentration(Cnmv/rtv) data (n = 114) of COVID-19 patients over 18 years old were collected from May 2022 to July 2022, and the results of the patients were retrospectively compared. According to the analysis of the early study of NMV/RTV, combined with the research results at home and abroad, according to whether the measured drug concentration > 987 ng/ml, the patients were divided into target group and non-target group,The non-target group was defined as not reaching the trough concentration level.

RESULTS

Serum NMV/RTV concentration in adult patients was correlated with prognostic nutritional index [PNI, (P < 0.05)], height (P < 0.05), weight (P < 0.05) and creatinine clearance [Crcl, (P < 0.05)]. Multivariate analysis showed that height, weight, PNI, lymphocyte (LYM) and CrCl were independent influencing factors of NMV/RTV trough concentration. However, after the correction of BMI calculation, there was no correlation between NMV/RTV and BMI, so in the clinical medication plan, the drug was not adjusted according to the height and weight.

CONCLUSIONS

The serum NMV/RTV concentration of adult patients gradually decreased with the increase of CrCl. For patients with high and low CrCl, the trough concentration of NMV/RTV should be continuously monitored and the dosing regimen should be adjusted to achieve the target trough concentration in these patients to reduce the effect of CrCl. PNI is also a key factor affecting drug concentration. For poor nutritional status, drug concentration should be closely monitored and the dose should be adjusted.

摘要

背景

在抗病毒治疗领域,有效的治疗浓度有利于缩短患者康复时间并降低传播率。本研究旨在回顾性分析导致奈玛特韦/利托那韦(NMV/RTV)药物浓度未达标的因素。

方法

本研究收集了2022年5月至2022年7月期间18岁以上新冠患者的NMV/RTV药物浓度(Cnmv/rtv)数据(n = 114),并对患者结果进行回顾性比较。根据NMV/RTV早期研究分析,结合国内外研究结果,根据所测药物浓度是否>987 ng/ml,将患者分为目标组和非目标组,非目标组定义为未达到谷浓度水平。

结果

成年患者血清NMV/RTV浓度与预后营养指数[PNI,(P < 0.05)]、身高(P < 0.05)、体重(P < 0.05)和肌酐清除率[Crcl,(P < 0.05)]相关。多因素分析显示,身高、体重、PNI、淋巴细胞(LYM)和CrCl是NMV/RTV谷浓度的独立影响因素。然而,校正BMI计算后,NMV/RTV与BMI无相关性,因此在临床用药方案中,未根据身高和体重调整药物。

结论

成年患者血清NMV/RTV浓度随CrCl升高而逐渐降低。对于CrCl高和低的患者,应持续监测NMV/RTV的谷浓度并调整给药方案,以在这些患者中达到目标谷浓度,降低CrCl的影响。PNI也是影响药物浓度的关键因素。对于营养状况差的患者,应密切监测药物浓度并调整剂量。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a55c/11653860/9489e329996e/12879_2024_10291_Fig1_HTML.jpg

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