{"title":"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","authors":"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","doi":"10.1111/fcp.12972","DOIUrl":null,"url":null,"abstract":"<div>\n \n \n <section>\n \n <h3> Background</h3>\n \n <p>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.</p>\n </section>\n \n <section>\n \n <h3> Objective</h3>\n \n <p>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.</p>\n </section>\n \n <section>\n \n <h3> Trial design</h3>\n \n <p>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).</p>\n </section>\n \n <section>\n \n <h3> Materials and methods</h3>\n \n <p>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.</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p>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<sub>max</sub> = 8008.33 (1042.25, 41081.11) ng/mL, AUC<sub>0-t</sub> = 4172.37 (904.42, 13912.61) ng/mL * h, AUC<sub>0-∞</sub> = 6712.85 (1856.77, 19971.12) ng/mL * h, T<sub>1/2</sub> = 1.22 (0.59, 2.83) h, T<sub>max</sub> = 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).</p>\n </section>\n \n <section>\n \n <h3> Conclusions</h3>\n \n <p>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.</p>\n </section>\n </div>","PeriodicalId":12657,"journal":{"name":"Fundamental & Clinical Pharmacology","volume":null,"pages":null},"PeriodicalIF":2.1000,"publicationDate":"2023-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"An exploratory study of drug concentration and inhibitory effect of cetylpyridinium chloride buccal tablets on SARS-CoV-2 infection among 10 Chinese subjects\",\"authors\":\"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\",\"doi\":\"10.1111/fcp.12972\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div>\\n \\n \\n <section>\\n \\n <h3> Background</h3>\\n \\n <p>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.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Objective</h3>\\n \\n <p>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.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Trial design</h3>\\n \\n <p>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).</p>\\n </section>\\n \\n <section>\\n \\n <h3> Materials and methods</h3>\\n \\n <p>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.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Results</h3>\\n \\n <p>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<sub>max</sub> = 8008.33 (1042.25, 41081.11) ng/mL, AUC<sub>0-t</sub> = 4172.37 (904.42, 13912.61) ng/mL * h, AUC<sub>0-∞</sub> = 6712.85 (1856.77, 19971.12) ng/mL * h, T<sub>1/2</sub> = 1.22 (0.59, 2.83) h, T<sub>max</sub> = 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).</p>\\n </section>\\n \\n <section>\\n \\n <h3> Conclusions</h3>\\n \\n <p>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.</p>\\n </section>\\n </div>\",\"PeriodicalId\":12657,\"journal\":{\"name\":\"Fundamental & Clinical Pharmacology\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":2.1000,\"publicationDate\":\"2023-11-20\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Fundamental & Clinical Pharmacology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1111/fcp.12972\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"PHARMACOLOGY & PHARMACY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Fundamental & Clinical Pharmacology","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1111/fcp.12972","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
An exploratory study of drug concentration and inhibitory effect of cetylpyridinium chloride buccal tablets on SARS-CoV-2 infection among 10 Chinese subjects
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: 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. 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.
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.
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