An exploratory study of drug concentration and inhibitory effect of cetylpyridinium chloride buccal tablets on SARS-CoV-2 infection among 10 Chinese subjects

IF 2.1 4区医学 Q3 PHARMACOLOGY & PHARMACY

Fundamental & Clinical Pharmacology Pub Date : 2023-11-20 DOI:10.1111/fcp.12972

Yanting Li, Zhenwei Xie, Liming Chen, Xiangxing Liu, Shuang Li, Shichun Ye, Hongyan Tang, Chongyou Lee, Qun Gu, Fang Men, Jiaojiao Zhang, Dingyuan Hu, Yuanli Jiang, Xiaochun Wang, Qian Wang, Yufei Feng, Suping Niu, Yan Liu, Yi Fang

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引用次数: 0

Abstract

Background

It was evidenced that cetylpyridinium-chloride (CPC) mouthwash could inhibit SARS-COV-2 activity and reduce salivary viral load, thus reducing SARS-CoV-2 transmission. However, due to insufficient residence time in the oral cavity, CPC-containing mouthwashes have no prolonged antiviral effect. The duration of action of the CPC buccal tablet is expected to be longer than that of the mouthwash. However, there are currently no reports on the salivary drug concentration of CPC buccal tablets.

Objective

The study aimed to investigate the salivary drug concentration of CPC buccal tablets and the antiviral effect of CPC on SARS-CoV-2 in vitro.

Trial design

This is a single-dose, single-arm clinical trial, involving 10 Chinese healthy subjects who received 2-mg CPC buccal tablet to collect saliva samples and to detect saliva concentration at different timepoints within 2 h (Clinical Trial Registration Number: NCT05802628, Registration Date: April 6, 2023).

Materials and methods

CPC concentration in saliva was detected by liquid chromatography tandem mass spectrometry (LC–MS/MS), and pharmacokinetic parameters were calculated based on the non-compartmental model. With an in vitro antiviral experiment, the activity of CPC buccal tablets against SARS-CoV-2 and its cellular toxicity was tested.

Results

Drug concentrations in saliva at 15 min, 30 min, 1 h, 1.5 h, and 2 h after administration were 8008.33 (1042.25, 41081.11), 2093.34 (373.15, 5759.83), 1016.58 (378.66, 3480.68), 891.77 (375.66, 6322.07), and 717.43 (197.87, 2152.71) ng/mL. PK parameters of saliva concentration: C_max = 8008.33 (1042.25, 41081.11) ng/mL, AUC_0-t = 4172.37 (904.42, 13912.61) ng/mL * h, AUC_0-∞ = 6712.85 (1856.77, 19971.12) ng/mL * h, T_1/2 = 1.22 (0.59, 2.83) h, T_max = 0.25 (0.25, 0.25) h. As determined in in vitro experiment, CPC was active on SARS-CoV-2 with cytotoxic and inhibitory activity of CC50 = 35.75 μM (≈12155 ng/mL) and EC50 = 7.39 μM (≈2512.6 ng/mL).

Conclusions

The comparison between the salivary CPC concentration and EC50/CC50 values from in vitro antiviral experiments suggests that CPC buccal tablets may inhibit SARS-CoV-2 activity, and the inhibition may last for approximately 30 min without cytotoxicity.

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氯代十六烷基吡啶含片药物浓度及对10例中国人SARS-CoV-2感染抑制作用的探索性研究

背景:十六烷基氯吡啶(CPC)漱口水可以抑制SARS-COV-2活性，降低唾液病毒载量，从而减少SARS-COV-2的传播。然而，由于在口腔内停留时间不足，含cpc漱口水没有持久的抗病毒效果。CPC含片的作用时间预计比漱口水的作用时间长。然而，目前还没有关于CPC含片唾液药物浓度的报道。目的:研究复方中药材含片的唾液药浓度及复方中药材对SARS-CoV-2的体外抗病毒作用。试验设计:本试验为单剂量、单臂临床试验，10名中国健康受试者接受2 mg CPC口腔片，采集唾液样本，检测2 h内不同时间点唾液浓度(临床试验注册号:NCT05802628，注册日期:2023年4月6日)。材料与方法:采用液相色谱-串联质谱法(LC-MS/MS)检测唾液中CPC浓度，并基于非室室模型计算药动学参数。通过体外抗病毒实验，检测了CPC口腔片对SARS-CoV-2的抗病毒活性及其细胞毒性。结果:给药后15 min、30 min、1 h、1.5 h、2 h唾液中药物浓度分别为8008.33(1042.25、41081.11)、2093.34(373.15、5759.83)、1016.58(378.66、3480.68)、891.77(375.66、6322.07)、717.43(197.87、2152.71)ng/mL。唾液浓度PK参数:Cmax = 8008.33 (1042.25, 41081.11) ng/mL, AUC0-t = 4172.37 (904.42, 13912.61) ng/mL * h, AUC0-∞= 6712.85 (1856.77,19971.12)ng/mL * h, T1/2 = 1.22 (0.59, 2.83) h, Tmax = 0.25 (0.25, 0.25) h。体外实验表明，CPC对SARS-CoV-2具有细胞毒活性，CC50 = 35.75 μM(≈12155 ng/mL)， EC50 = 7.39 μM(≈2512.6 ng/mL)。结论:体外抗病毒实验中唾液CPC浓度和EC50/CC50值的比较表明，CPC口腔片可抑制SARS-CoV-2活性，且抑制时间约为30 min，无细胞毒性。

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

Fundamental & Clinical Pharmacology 医学-药学

CiteScore

5.30

自引率

6.90%

发文量

111

审稿时长

6-12 weeks

期刊介绍： Fundamental & Clinical Pharmacology publishes reports describing important and novel developments in fundamental as well as clinical research relevant to drug therapy. Original articles, short communications and reviews are published on all aspects of experimental and clinical pharmacology including: Antimicrobial, Antiviral Agents Autonomic Pharmacology Cardiovascular Pharmacology Cellular Pharmacology Clinical Trials Endocrinopharmacology Gene Therapy Inflammation, Immunopharmacology Lipids, Atherosclerosis Liver and G-I Tract Pharmacology Metabolism, Pharmacokinetics Neuropharmacology Neuropsychopharmacology Oncopharmacology Pediatric Pharmacology Development Pharmacoeconomics Pharmacoepidemiology Pharmacogenetics, Pharmacogenomics Pharmacovigilance Pulmonary Pharmacology Receptors, Signal Transduction Renal Pharmacology Thrombosis and Hemostasis Toxicopharmacology Clinical research, including clinical studies and clinical trials, may cover disciplines such as pharmacokinetics, pharmacodynamics, pharmacovigilance, pharmacoepidemiology, pharmacogenomics and pharmacoeconomics. Basic research articles from fields such as physiology and molecular biology which contribute to an understanding of drug therapy are also welcomed.