Camostat mesylate is expected to be promising as a treatment option for COVID-19, in addition to other indications for which it is currently used. Furthermore, in vitro experiments have confirmed the potential of camostat and its metabolites to be effective against COVID-19. Therefore, clinical trials were conducted to evaluate the safety and pharmacokinetic characteristics of camostat after single-dose administration. Additionally, we aim to predict the pharmacokinetics of repeated dosing through modeling and simulation based on clinical trials. Clinical trials were conducted on healthy Korean adults, and an analysis was carried out of the metabolites of camostat, GBPA, and GBA. Pharmacokinetic modeling and simulation were performed using Monolix. There were no safety issues (AEs, physical examinations, clinical laboratory tests, vital sign measurements, and ECG) during the clinical trial. The pharmacokinetic characteristics at various doses were identified. It was confirmed that AUC last and Cmax increased in proportion to dose in both GBPA and GBA, and linearity was also confirmed in log-transformed power model regression. Additionally, the accumulation index was predicted (1.12 and 1.08 for GBPA and GBA). The pharmacokinetics of camostat for various dose administrations and indications can be predicted prior to clinical trials using the developed camostat model. Furthermore, it can be used for various indications by connecting it with pharmacodynamic information.

中文翻译：

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使用 I 期研究对甲磺酸卡莫司他及其主要代谢物进行安全性评价和群体药代动力学

除了目前使用的其他适应症之外，甲磺酸卡莫司他预计有望作为 COVID-19 的治疗选择。此外，体外实验已证实卡莫司他及其代谢物具有有效对抗 COVID-19 的潜力。因此，进行了临床试验来评估单剂量给药后卡莫司他的安全性和药代动力学特征。此外，我们的目标是通过基于临床试验的建模和模拟来预测重复给药的药代动力学。对健康的韩国成年人进行了临床试验，并对卡莫司他、GBPA 和 GBA 的代谢物进行了分析。使用 Monolix 进行药代动力学建模和模拟。临床试验期间没有出现安全问题（AE、体检、临床实验室测试、生命体征测量和心电图）。确定了不同剂量下的药代动力学特征。已证实，GBPA 和 GBA 中 AUC Last 和 Cmax 均与剂量成比例增加，并且在对数转换功效模型回归中也证实了线性。此外，还预测了累积指数（GBPA 和 GBA 为 1.12 和 1.08）。可以在临床试验之前使用开发的卡莫司他模型预测不同剂量给药和适应症的卡莫司他药代动力学。此外，通过与药效信息连接，可用于各种适应症。