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

• Published in: Fundamental & clinical pharmacology Vol. 38; no. 3; pp. 579 - 587
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: England Wiley Subscription Services, Inc 01.06.2024
• Subjects: Administration, Buccal; Adult; Antiviral agents; Antiviral Agents - administration & dosage; Antiviral Agents - pharmacokinetics; Antiviral Agents - pharmacology; Cetylpyridinium; Cetylpyridinium chloride; China; Chlorides; Chromatography; Clinical trials; COVID-19; COVID-19 Drug Treatment; Cytotoxicity; Drugs; Female; Humans; Liquid chromatography; Male; Mass spectrometry; Mass spectroscopy; Mouthwashes; Oral cavity; Parameters; Pharmacokinetics; Residence time; Saliva; SARS-CoV-2 - drug effects; Severe acute respiratory syndrome; Severe acute respiratory syndrome coronavirus 2; Tablets; Toxicity testing; Viral diseases; Viral Load - drug effects; Young Adult; China; SARS‐CoV‐2; antiviral agents; pharmacokinetics clinical trial
• ISSN: 0767-3981; 1472-8206; 1472-8206
• DOI: 10.1111/fcp.12972

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. 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. 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). 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. 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  = 8008.33 (1042.25, 41081.11) ng/mL, AUC  = 4172.37 (904.42, 13912.61) ng/mL * h, AUC  = 6712.85 (1856.77, 19971.12) ng/mL * h, T  = 1.22 (0.59, 2.83) h, T  = 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). 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.