Peking University Peoples Hospital, Beijing, China.
Chongqing Jewelland Pharmaceutical Co., Ltd, Chongqing, China.
Fundam Clin Pharmacol. 2024 Jun;38(3):579-587. doi: 10.1111/fcp.12972. Epub 2023 Nov 20.
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.
已有证据表明，氯化十六烷基吡啶（CPC）漱口水可以抑制 SARS-CoV-2 的活性并降低唾液中的病毒载量，从而降低 SARS-CoV-2 的传播。然而，由于在口腔内的停留时间不足，含 CPC 的漱口水没有延长的抗病毒作用。CPC 口颊片的作用持续时间预计会比漱口水更长。但是，目前尚无 CPC 口颊片在唾液中的药物浓度的报告。
本研究旨在探讨 CPC 口颊片的唾液药物浓度以及 CPC 对 SARS-CoV-2 的体外抗病毒作用。
这是一项单剂量、单臂临床试验，涉及 10 名中国健康受试者，他们接受 2 毫克 CPC 口颊片以收集唾液样本，并在 2 小时内的不同时间点（临床试验注册号：NCT05802628，登记日期：2023 年 4 月 6 日）检测唾液浓度。
采用液相色谱串联质谱法（LC-MS/MS）检测唾液中的 CPC 浓度，并基于非房室模型计算药代动力学参数。通过体外抗病毒实验，测试 CPC 口颊片对 SARS-CoV-2 的活性及其细胞毒性。
给药后 15 分钟、30 分钟、1 小时、1.5 小时和 2 小时唾液中的药物浓度分别为 8008.33（1042.25，41081.11）、2093.34（373.15，5759.83）、1016.58（378.66，3480.68）、891.77（375.66，6322.07）和 717.43（197.87，2152.71）ng/mL。唾液浓度的 PK 参数：C=8008.33（1042.25，41081.11）ng/mL，AUC=4172.37（904.42，13912.61）ng/mLh，AUC=6712.85（1856.77，19971.12）ng/mLh，T=1.22（0.59，2.83）h，T=0.25（0.25，0.25）h。在体外实验中确定，CPC 对 SARS-CoV-2 具有活性，具有细胞毒性和抑制活性，CC50=35.75 μM（≈12155 ng/mL）和 EC50=7.39 μM（≈2512.6 ng/mL）。
唾液中 CPC 浓度与体外抗病毒实验中的 EC50/CC50 值的比较表明，CPC 口颊片可能抑制 SARS-CoV-2 的活性，抑制作用可持续约 30 分钟，且无细胞毒性。
