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

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

作者地址："[Li, Yanting; Xie, Zhenwei; Chen, Liming; Liu, Xiangxing; Li, Shuang; Lee, Chongyou; Gu, Qun; Men, Fang; Zhang, Jiaojiao; Hu, Dingyuan; Wang, Qian; Feng, Yufei; Niu, Suping; Fang, Yi] Peking Univ Peoples Hosp, Beijing, Peoples R China; [Ye, Shichun; Tang, Hongyan] Chongqing Jewelland Pharmaceut Co Ltd, Chongqing, Peoples R China; [Jiang, Yuanli; Wang, Xiaochun] Zunyi Med Univ, Affiliated Hosp, Zunyi, Peoples R China; [Liu, Yan] Chongqing Med Univ, Chongqing, Peoples R China; [Feng, Yufei; Niu, Suping; Fang, Yi] Peking Univ Peoples Hosp, Beijing 100044, Peoples R China; [Liu, Yan] Chongqing Med Univ, Chongqing 400016, Peoples R China"

通信作者："Feng, YF; Niu, SP; Fang, Y (通讯作者)，Peking Univ Peoples Hosp, Beijing 100044, Peoples R China.; Liu, Y (通讯作者)，Chongqing Med Univ, Chongqing 400016, Peoples R China."

来源：FUNDAMENTAL & CLINICAL PHARMACOLOGY

ESI学科分类：PHARMACOLOGY & TOXICOLOGY

WOS号：WOS:001104540100001

JCR分区：Q3

影响因子：2.1

年份：2023

卷号：　

期号：　

开始页：　

结束页：　

文献类型：Article; Early Access

关键词：antiviral agents; pharmacokinetics clinical trial; SARS-CoV-2

摘要："BackgroundIt 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.ObjectiveThe 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 designThis 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 methodsCPC 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.ResultsDrug 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-infinity = 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 mu M (approximate to 12155 ng/mL) and EC50 = 7.39 mu M (approximate to 2512.6 ng/mL).ConclusionsThe 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."

基金机构："We acknowledge support of Peking University Peoples Hospital in project executing and writing. The authors also would like to thank the financial support of Peking University Peopleapos;s Hospital Scientific Research Development Funds (Project RDN2022-28) [RDN2022-28]; Peking University Peopleapos;s Hospital Scientific Research Development Funds; Chongqing Jewelland Pharmaceutical Co., Ltd."

基金资助正文："We acknowledge support of Peking University Peoples Hospital in project executing and writing. The authors also would like to thank the financial support of Peking University People & apos;s Hospital Scientific Research Development Funds (Project RDN2022-28) and Chongqing Jewelland Pharmaceutical Co., Ltd."