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Journal of Zhejiang University SCIENCE B

ISSN 1673-1581(Print), 1862-1783(Online), Monthly

Pharmacokinetic interactions between the potential COVID-19 treatment drugs lopinavir/ritonavir and arbidol in rats

Abstract: The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has occasioned worldwide alarm. Globally, the number of reported confirmed cases has exceeded 84.3 million as of this writing (January 2, 2021). Since there are no targeted therapies for COVID-19, the current focus is the repurposing of drugs approved for other uses. In some clinical trials, antiviral drugs such as remdesivir (Grein et al., 2020), lopinavir/ritonavir (LPV/r) (Cao et al., 2020), chloroquine (Gao et al., 2020), hydroxychloroquine (Gautret et al., 2020), arbidol (Wang et al., 2020), and favipiravir (Cai et al., 2020b) have shown efficacy in COVID-19 patients. LPV/r combined with arbidol, which is the basic regimen in some regional hospitals in China including Zhejiiang Province, has shown antiviral effects in COVID-19 patients (Guo et al., 2020; Xu et al., 2020). A retrospective cohort study also reported that this combination therapy showed better efficacy than LPV/r alone for the treatment of COVID-19 patients (Deng et al., 2020).

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Chinese Summary  <32> COVID-19潜在治疗药物洛匹那韦/利托那韦和阿比多尔在大鼠体内的药代动力学相互作用

目的:研究抗病毒药物洛匹那韦/利托那韦和阿比多尔在大鼠体内的药代动力学相互作用。
创新点:洛匹那韦/利托那韦联合阿比多尔作为国内多家医疗单位治疗COVID-19患者的基础抗病毒方案,两者的药物相互作用未有研究报道,本论文通过开展体内药动学实验,探索合用后药物体内暴露量的改变,为该方案的临床治疗有效性和安全性提供保障。
方法:建立大鼠洛匹那韦/利托那韦与阿比多尔药动学相互作用模型。将大鼠分为3组(阿比多尔组、洛匹那韦/利托那韦组及联用组)。洛匹那韦/利托那韦和阿比多尔分别以50mg/kg/12.5 mg/kg和25 mg/kg灌胃给药。采用液相色谱串联质谱(LC-MS/MS)法测定洛匹那韦和阿比多尔的浓度。
结论:洛匹那韦/利托那韦联合阿比多尔治疗后,阿比多尔的药时曲线下面积(AUC)和洛匹那韦的峰浓度(Cmax)显著升高。这两种药物的相互作用可能会影响联合治疗的安全性。因此,洛匹那韦/利托那韦与阿比多尔同时给药时,建议适当调整给药剂量,阿比多尔的剂量可能需要减半。

关键词组:药代动力学;COVID-19;相互作用;洛匹那韦/利托那韦;阿比多尔


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DOI:

10.1631/jzus.B2000728

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On-line Access:

2024-08-27

Received:

2023-10-17

Revision Accepted:

2024-05-08

Crosschecked:

2022-04-22

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