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

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    • Source:
      Publisher: Blackwell Science Country of Publication: England NLM ID: 8710411 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1472-8206 (Electronic) Linking ISSN: 07673981 NLM ISO Abbreviation: Fundam Clin Pharmacol Subsets: MEDLINE
    • Publication Information:
      Publication: <2001->: Oxford : Blackwell Science
      Original Publication: Paris ; New York : Elsevier, c1987-
    • Subject Terms:
    • 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.
      (© 2023 Société Française de Pharmacologie et de Thérapeutique. Published by John Wiley & Sons Ltd.)
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    • Grant Information:
      RDN2022-28 Peking University People's Hospital Scientific Research Development Funds; Chongqing Jewelland Pharmaceutical Co., Ltd.
    • Contributed Indexing:
      Keywords: SARS‐CoV‐2; antiviral agents; pharmacokinetics clinical trial
    • Molecular Sequence:
      ClinicalTrials.gov NCT05802628
    • Accession Number:
      CUB7JI0JV3 (Cetylpyridinium)
      0 (Tablets)
      0 (Antiviral Agents)
      0 (Mouthwashes)
    • Publication Date:
      Date Created: 20231121 Date Completed: 20240514 Latest Revision: 20240521
    • Publication Date:
      20240521
    • Accession Number:
      10.1111/fcp.12972
    • Accession Number:
      37985697