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

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

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

Fundam Clin Pharmacol. 2023 Nov 20. doi: 10.1111/fcp.12972. Online ahead of print.

Authors

Yanting Li¹, Zhenwei Xie¹, Liming Chen¹, Xiangxing Liu¹, Shuang Li¹, Shichun Ye², Hongyan Tang², Chongyou Lee¹, Qun Gu¹, Fang Men¹, Jiaojiao Zhang¹, Dingyuan Hu¹, Yuanli Jiang³, Xiaochun Wang³, Qian Wang¹, Yufei Feng¹, Suping Niu¹, Yan Liu⁴, Yi Fang¹

Affiliations

¹ Peking University Peoples Hospital, Beijing, China.
² Chongqing Jewelland Pharmaceutical Co., Ltd, Chongqing, China.
³ Affiliated Hospital of Zunyi Medical University, Zunyi, China.
⁴ Chongqing Medical University, Chongqing, China.

PMID: 37985697
DOI: 10.1111/fcp.12972

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.

Keywords: SARS-CoV-2; antiviral agents; pharmacokinetics clinical trial.

Associated data

ClinicalTrials.gov/NCT05802628

Abstract

Associated data

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