BACKGROUND 2-Hydroxybenzylamine (2-HOBA) is a selective dicarbonyl electrophile scavenger being developed as a nutritional supplement to help protect against the development of conditions associated with dicarbonyl electrophile formation, such as the cognitive decline observed with Mild Cognitive Impairment or Alzheimer's disease. METHODS This study evaluated the safety, tolerability, and pharmacokinetics of repeated oral doses of 2-HOBA acetate (500 or 750 mg) administered to healthy volunteers every eight hours for two weeks. The effects of 2-HOBA on cyclooxygenase function and cerebrospinal fluid penetrance of 2-HOBA were also investigated. RESULTS Repeated oral administration of 2-HOBA was found to be safe and well-tolerated up to 750 mg TID for 15 days. 2-HOBA was absorbed within 2 h of administration, had a half-life of 2.10-3.27 h, and an accumulation ratio of 1.38-1.52. 2-HOBA did not interfere with cyclooxygenase function and was found to be present in cerebrospinal fluid 90 min after dosing. CONCLUSIONS Repeated oral administration of 2-HOBA was found to be safe and well-tolerated. These results support continued development of 2-HOBA as a nutritional supplement. TRIAL REGISTRATION Studies are registered at ClinicalTrials.gov (NCT03555682 Registered 13 June 2018, NCT03554096 Registered 12 June 18).

中文翻译：

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健康志愿者重复口服剂量的 2-羟基苄胺乙酸酯的安全性、耐受性和药代动力学：一项双盲、随机、安慰剂对照临床试验。


背景 2-羟基苄胺 (2-HOBA) 是一种选择性二羰基亲电体清除剂，被开发为营养补充剂，以帮助预防与二羰基亲电体形成相关的疾病的发展，例如在轻度认知障碍或阿尔茨海默氏病中观察到的认知能力下降。方法 本研究评估了健康志愿者每 8 小时重复口服 2-HOBA 醋酸盐（500 或 750 mg）的安全性、耐受性和药代动力学，持续两周。还研究了 2-HOBA 对环氧合酶功能和 2-HOBA 脑脊液渗透性的影响。结果发现重复口服 2-HOBA 是安全的，并且耐受性良好，每次 750 mg TID，持续 15 天。 2-HOBA在给药后2小时内被吸收，半衰期为2.10-3.27小时，蓄积比为1.38-1.52。 2-HOBA 不会干扰环氧合酶功能，并且在给药后 90 分钟发现其存在于脑脊液中。结论 重复口服 2-HOBA 被发现是安全且耐受性良好的。这些结果支持 2-HOBA 作为营养补充剂的持续开发。试验注册 研究已在 ClinicalTrials.gov 上注册（NCT03555682 于 2018 年 6 月 13 日注册，NCT03554096 于 2018 年 6 月 12 日注册）。