■脑损伤是院外心脏骤停(OHCA)患者的严重问题。神经保护药物可减轻缺氧缺血再灌注损伤。这项研究的目的是调查安全性,耐受性,和2-亚氨基生物素(2-IB)的药代动力学(PK),神经元一氧化氮合酶的选择性抑制剂。
■单中心,成人OHCA患者的开放标签剂量递增研究,调查三个2-IB给药时间表(目标是队列A中600-1,200ng*h/m的AUC0-24h,队列B中的2,100-3,300ng*h/mL,和队列C中的7,200-8,400ng*h/mL)。通过监测生命体征直到研究药物施用后15分钟以及入院后30天的不良事件来研究安全性。进行血液取样用于PK分析。OHCA后30天收集脑生物标志物和患者结果。
■共纳入21名患者,队列A和B中有8个,队列C中有5个。没有观察到生命体征的变化,未报告与2-IB相关的不良事件.两室PK模型最好地描述了数据。A组的暴露(按体重给药)比目标(中位数AUC0-24小时2,398ng*h/mL)高三倍。肾功能是一个重要的协变量;因此,在队列B中,入院时对eGFR进行给药。在队列B和C中,目标暴露得到满足(中位数AUC0-24h2,917和7,323ng*h/mL,分别)。
■OHCA后对成人施用2-IB是可行且安全的。通过校正入院时的肾功能,可以很好地预测PK。OHCA后需要2-IB的疗效研究。
UNASSIGNED: Brain injury is a serious problem in patients who survive out-of-hospital cardiac arrest (OHCA). Neuroprotective drugs could reduce hypoxic-ischemic reperfusion injury. The aim of this
study was to investigate the safety, tolerability, and pharmacokinetics (PK) of 2-iminobiotin (2-IB), a selective inhibitor of neuronal nitric oxide synthase.
UNASSIGNED: Single-center, open-label dose-escalation
study in adult OHCA patients, investigating three 2-IB dosing schedules (targeting an AUC0-24h of 600-1,200 ng*h/m in cohort A, of 2,100-3,300 ng*h/mL in cohort B, and 7,200-8,400 of ng*h/mL in cohort C). Safety was investigated by monitoring vital signs until 15 min after
study drug administration and adverse events up to 30 days after admission. Blood sampling for PK analysis was performed. Brain biomarkers and patient outcomes were collected 30 days after OHCA.
UNASSIGNED: A total of 21 patients was included, eight in cohort A and B and five in cohort C. No changes in vital signs were observed, and no adverse events related to 2-IB were reported. A two-compartment PK model described data the best. Exposure in group A (dosed on bodyweight) was three times higher than targeted (median AUC0-24h 2,398 ng*h/mL). Renal function was an important covariate; therefore, in cohort B, dosing was performed on eGFR on admission. In cohort B and C, the targeted exposure was met (median AUC0-24h 2,917 and 7,323 ng*h/mL, respectively).
UNASSIGNED: The administration of 2-IB to adults after OHCA is feasible and safe. PK can be well predicted with correction for renal function on admission. Efficacy studies with 2-IB after OHCA are needed.