Full Text:   <1399>

Summary:  <1432>

CLC number: 

On-line Access: 2022-04-22

Received: 2021-01-03

Revision Accepted: 2021-02-21

Crosschecked: 2022-04-22

Cited: 0

Clicked: 2988

Citations:  Bibtex RefMan EndNote GB/T7714

 ORCID:

Saiping JIANG

https://orcid.org/0000-0001-7720-2725

-   Go to

Article info.
Open peer comments

Journal of Zhejiang University SCIENCE B 2021 Vol.22 No.7 P.599-602

http://doi.org/10.1631/jzus.B2000728


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


Author(s):  Yunzhen HU, Minjuan ZUO, Xiaojuan WANG, Rongrong WANG, Lu LI, Xiaoyang LU, Saiping JIANG

Affiliation(s):  Department of Clinical Pharmacy, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310006, China; more

Corresponding email(s):   j5145@zju.edu.cn

Key Words: 


Yunzhen HU, Minjuan ZUO, Xiaojuan WANG, Rongrong WANG, Lu LI, Xiaoyang LU, Saiping JIANG. Pharmacokinetic interactions between the potential COVID-19 treatment drugs lopinavir/ritonavir and arbidol in rats[J]. Journal of Zhejiang University Science B, 2021, 22(7): 599-602.

@article{title="Pharmacokinetic interactions between the potential COVID-19 treatment drugs lopinavir/ritonavir and arbidol in rats",
author="Yunzhen HU, Minjuan ZUO, Xiaojuan WANG, Rongrong WANG, Lu LI, Xiaoyang LU, Saiping JIANG",
journal="Journal of Zhejiang University Science B",
volume="22",
number="7",
pages="599-602",
year="2021",
publisher="Zhejiang University Press & Springer",
doi="10.1631/jzus.B2000728"
}

%0 Journal Article
%T Pharmacokinetic interactions between the potential COVID-19 treatment drugs lopinavir/ritonavir and arbidol in rats
%A Yunzhen HU
%A Minjuan ZUO
%A Xiaojuan WANG
%A Rongrong WANG
%A Lu LI
%A Xiaoyang LU
%A Saiping JIANG
%J Journal of Zhejiang University SCIENCE B
%V 22
%N 7
%P 599-602
%@ 1673-1581
%D 2021
%I Zhejiang University Press & Springer
%DOI 10.1631/jzus.B2000728

TY - JOUR
T1 - Pharmacokinetic interactions between the potential COVID-19 treatment drugs lopinavir/ritonavir and arbidol in rats
A1 - Yunzhen HU
A1 - Minjuan ZUO
A1 - Xiaojuan WANG
A1 - Rongrong WANG
A1 - Lu LI
A1 - Xiaoyang LU
A1 - Saiping JIANG
J0 - Journal of Zhejiang University Science B
VL - 22
IS - 7
SP - 599
EP - 602
%@ 1673-1581
Y1 - 2021
PB - Zhejiang University Press & Springer
ER -
DOI - 10.1631/jzus.B2000728


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).

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:药代动力学;COVID-19;相互作用;洛匹那韦/利托那韦;阿比多尔

Darkslateblue:Affiliate; Royal Blue:Author; Turquoise:Article

Reference

[1]CaiQX, HuangDL, YuH, et al., 2020a. COVID-19: abnormal liver function tests. J Hepatol, 73(3):566-574.

[2]CaiQX, YangMH, LiuDJ, et al., 2020b. Experimental treatment with favipiravir for COVID-19: an open-label control study. Engineering (Beijing), 6(10):1192-1198.

[3]CaoB, WangYM, WenDN, et al., 2020. A trial of lopinavir-ritonavir in adults hospitalized with severe Covid-19. N Engl J Med, 382(19):1787-1799.

[4]DengLS, LiCN, ZengQ, et al., 2020. Arbidol combined with LPV/r versus LPV/r alone against corona virus disease 2019: a retrospective cohort study. J Infect, 81(1):E1-E5.

[5]GaoJJ, TianZX, YangX, 2020. Breakthrough: chloroquine phosphate has shown apparent efficacy in treatment of COVID-19 associated pneumonia in clinical studies. Biosci Trends, 14(1):72-73.

[6]GautretP, LagierJC, ParolaP, et al., 2020. Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial. Int J Antimicrob Agents, 56(1):105949.

[7]GreinJ, OhmagariN, ShinD, et al., 2020. Compassionate use of remdesivir for patients with severe Covid-19. N Engl J Med, 382(24):2327-2336.

[8]GuoYZ, XuKJ, LiYT, et al., 2020. Safety of protease inhibitors and Arbidol for SARS-CoV-2 pneumonia in Zhejiang Province, China. J Zhejiang Univ-Sci B (Biomed & Biotechnol), 21(12):948-954.

[9]JiangSP, WangRR, LiL, et al., 2020. Liver injury in critically ill and non-critically ill COVID-19 patients: a multicenter, retrospective, observational study. Front Med (Lausanne), 7:347.

[10]JullienV, UrienS, HirtD, et al., 2006. Population analysis of weight-, age-, and sex-related differences in the pharmacokinetics of lopinavir in children from birth to 18 years. Antimicrob Agents Chemother, 50(11):3548-3555.

[11]LiverTox, 2012. Clinical and research information on drug-induced liver injury: protease inhibitors (HIV). Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases. https://www.ncbi.nlm.nih.gov/books/NBK548893

[12]OfotokunI, ChuckSK, BinongoJN, et al., 2007. Lopinavir/ritonavir pharmacokinetic profile: impact of sex and other covariates following a change from twice-daily to once-daily therapy. J Clin Pharmacol, 47(8):970-977.

[13]UmehOC, CurrierJS, ParkJG, et al., 2011. Sex differences in lopinavir and ritonavir pharmacokinetics among HIV-infected women and men. J Clin Pharmacol, 51(12):1665-1673.

[14]WangZL, YangBH, LiQW, et al., 2020. Clinical features of 69 cases with coronavirus disease 2019 in Wuhan, China. Clin Infect Dis, 71(15):769-777.

[15]XuKJ, CaiHL, ShenYH, et al., 2020. Management of COVID-19: the Zhejiang experience. J Zhejiang Univ (Med Sci), 49(2):147-157 (in Chinese).

[16]ZhangC, ShiL, WangFS, 2020. Liver injury in COVID-19: management and challenges. Lancet Gastroenterol Hepatol, 5(5):428-430.

Open peer comments: Debate/Discuss/Question/Opinion

<1>

Please provide your name, email address and a comment





Journal of Zhejiang University-SCIENCE, 38 Zheda Road, Hangzhou 310027, China
Tel: +86-571-87952783; E-mail: cjzhang@zju.edu.cn
Copyright © 2000 - 2022 Journal of Zhejiang University-SCIENCE