洛匹那韦与利托那韦联合用药对COVID-19的药代动力学模拟:利托那韦强化洛匹那韦。

IF 1.8 4区 医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL
In vivo Pub Date : 2025-07-01 DOI:10.21873/invivo.14005
Yuta Nakamaru, Ken-Ichi Sako, Naohito Ide, Yoshikazu Matsuda, Fumiyoshi Yamashita, Tomoji Maeda
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引用次数: 0

摘要

背景/目的:洛匹那韦(LPV)联合利托那韦(LPV/r)最初用于治疗人类免疫缺陷病毒(HIV)感染,随后在COVID-19大流行期间被重新用于治疗冠状病毒病2019 (COVID-19)。由于LPV/r治疗COVID-19的疗效尚未在临床试验中得到证实,因此LPV/r未列入日本COVID-19治疗指南。此外,以前的临床研究并未证明LPV/r在治疗艾滋病毒感染的剂量相同的情况下对COVID-19有益处。因此,本研究的目的是确定治疗COVID-19的最佳LPV/r剂量组合。患者和方法:基于健康志愿者和HIV感染患者的数据,采用最大效应模型估计LPV清除率与利托那韦血药浓度之间的关系。药代动力学模拟使用基于先前报道的建模方程的一系列假设进行。结果:LPV/r标准剂量组合400mg / 100mg每日2次不能产生最佳血药浓度。根据利托那韦的药代动力学增强效应,估计最佳剂量组合为400mg LPV + 1200mg利托那韦。结论:本研究结果为量化利托那韦在COVID-19治疗中对LPV的增强作用以及计算LPV与利托那韦的最佳剂量组合提供了依据。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Pharmacokinetic Simulation of Optimal Lopinavir and Ritonavir Dose Combination for COVID-19: Boosting Lopinavir With Ritonavir.

Background/aim: Lopinavir (LPV) combined with ritonavir (LPV/r) was initially developed to treat human immunodeficiency virus (HIV) infection and was subsequently repurposed to treat coronavirus disease 2019 (COVID-19) during the COVID-19 pandemic. As the efficacy of LPV/r in COVID-19 treatment has not been confirmed in clinical trials, LPV/r is not included in the Japanese COVID-19 treatment guidelines. Furthermore, previous clinical studies have not demonstrated the benefit of LPV/r against COVID-19 when used at the same dose as that used to treat HIV infection. Therefore, the aim of this study was to determine the optimal LPV/r dose combination for COVID-19 treatment.

Patients and methods: Based on data from healthy volunteers and patients with HIV infection, maximum-effect models were used to estimate the relationship between LPV clearance and ritonavir plasma concentration. Pharmacokinetic simulations were performed using a range of assumptions based on previously reported modeling equations.

Results: The standard LPV/r dose combination of 400 mg/100 mg twice daily did not yield optimal blood concentrations. Based on the pharmacokinetic booster effect of ritonavir, the estimated optimal dose combination was 400 mg LPV boosted with 1,200 mg ritonavir.

Conclusion: These findings provide a basis to quantify the booster effect of ritonavir on LPV in COVID-19 treatment and calculate the optimal LPV and ritonavir dose combination.

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来源期刊
In vivo
In vivo 医学-医学:研究与实验
CiteScore
4.20
自引率
4.30%
发文量
330
审稿时长
3-8 weeks
期刊介绍: IN VIVO is an international peer-reviewed journal designed to bring together original high quality works and reviews on experimental and clinical biomedical research within the frames of physiology, pathology and disease management. The topics of IN VIVO include: 1. Experimental development and application of new diagnostic and therapeutic procedures; 2. Pharmacological and toxicological evaluation of new drugs, drug combinations and drug delivery systems; 3. Clinical trials; 4. Development and characterization of models of biomedical research; 5. Cancer diagnosis and treatment; 6. Immunotherapy and vaccines; 7. Radiotherapy, Imaging; 8. Tissue engineering, Regenerative medicine; 9. Carcinogenesis.
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