EFFECTS OF ST JOHN'S WORT ON PK AND PD OF INTRAVENOUS FENTANYL

圣约翰草对芬太尼静脉注射的 PK 和 PD 的影响

• 批准号: 7379325
• 负责人: DANNY D SHEN
• 金额: $ 0.25万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-04-01 至 2007-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7379325
• 关键词: EFFECTS; ST; JOHN; WORT; PK

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The overall objective of this research protocol is to investigate if a significant interaction occurs between a widely used opioid analgesic fentanyl, and the over-the-counter, natural antidepressant-St. John's wort (SJW) extract in healthy volunteers. We will investigate whether SJW pretreatment decreases the delivery of intravenously administered fentanyl to the brain and compromises its analgesic efficacy through an up-regulation of P-glycoprotein mediated efflux transport at the blood-brain barrier. Subjects will be randomly assigned to one of two treatment arms: placebo and active SJW. For each arm, subjects will receive intravenous fentanyl on two separate study days before and after at least 14 days of either placebo or SJW treatment. On the first study day, a fixed dose of fentanyl will be infused intravenously over 30 min. The rate of access and CNS availability of fentanyl will be assessed by following the effect of opioid on pupil size over time. In the second study day, fentanyl will be infused by means of a computer-controlled pump to achieve and maintain a target steady state plasma fentanyl concentration for four hours. Analgesic and side effects of opioid will be evaluated during steady-state fentanyl infusion. Results of this study should guide the clinical use of fentanyl, either for anesthesia or pain management, in patients who have been taking SJW for treatment of depression.

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。本研究方案的总体目标是调查在健康志愿者中广泛使用的阿片类镇痛药芬太尼和非处方天然抗抑郁药-圣约翰草（SJW）提取物之间是否发生显著的相互作用。我们将研究SJW预处理是否减少了静脉注射芬太尼到大脑的递送，并通过上调血脑屏障P-糖蛋白介导的外排转运而损害其镇痛功效。受试者将被随机分配至两个治疗组之一：安慰剂组和活性SJW组。对于每组，受试者将在安慰剂或SJW治疗至少14天之前和之后的两个单独的研究日接受静脉芬太尼。在研究的第一天，将在30分钟内静脉输注固定剂量的芬太尼。将通过跟踪阿片类药物对瞳孔大小随时间的影响来评估芬太尼的进入率和CNS可用性。在研究的第二天，将通过计算机控制的泵输注芬太尼，以达到并维持目标稳态血浆芬太尼浓度4小时。将在稳态芬太尼输注期间评价阿片类药物的镇痛和副作用。这项研究的结果应该指导临床使用芬太尼，无论是麻醉或疼痛管理，在患者谁一直服用SJW治疗抑郁症。