Okumura Hitoshi, Araragi Yudai, Nishioka Kentaro, Yamashita Reiya, Suzuki Toshihide, Watanabe Hiroshi, Kato Yukio, Murayama Norihito
Research Institute Suntory Global Innovation Center Ltd. Kyoto Japan.
Faculty of Pharmacy Kanazawa University Kanazawa Japan.
Food Sci Nutr. 2025 Jun 5;13(6):e70382. doi: 10.1002/fsn3.70382. eCollection 2025 Jun.
A four-week administration of 20 mg/day ergothioneine (EGT), a strong antioxidant, improves sleep quality; however, its effect at lower doses remains unclear. This study estimated the lower effective doses of EGT using a physiologically based pharmacokinetic (PBPK) model in two clinical trials. In Study 1, participants received 5 or 10 mg/day of EGT for 8 weeks, and their plasma and blood EGT concentrations were measured. An optimized PBPK model incorporating absorption, distribution, and excretion was assembled. Our results showed that 8 mg/day of EGT for 16 weeks was optimal for attaining an effective plasma EGT concentration. In Study 2, a randomized, double-blind, placebo-controlled study, participants received 8 mg/day EGT or a placebo for 16 weeks. The subjective sleep quality was significantly improved in the EGT group than in the placebo group ( < 0.05). This is the first study to propose a strategy to estimate lower effective doses based on the PBPK model.
连续四周每天服用20毫克麦角硫因（EGT，一种强抗氧化剂）可改善睡眠质量；然而，其较低剂量的效果仍不明确。本研究在两项临床试验中使用基于生理的药代动力学（PBPK）模型估计了EGT的较低有效剂量。在研究1中，参与者连续8周每天服用5或10毫克EGT，并测量其血浆和血液中的EGT浓度。构建了一个包含吸收、分布和排泄的优化PBPK模型。我们的结果表明，连续16周每天服用8毫克EGT最有利于达到有效的血浆EGT浓度。在研究2中，一项随机、双盲、安慰剂对照研究中，参与者连续16周每天服用8毫克EGT或安慰剂。EGT组的主观睡眠质量显著优于安慰剂组（<0.05）。这是第一项提出基于PBPK模型估计较低有效剂量策略的研究。
