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。子弹和调查员（PI）可能已经从其他NIH来源获得了主要资金，因此可以在其他清晰的条目中代表。列出的机构适用于该中心，这不一定是调查员的机构。该研究方案的总体目的是研究广泛使用的阿片类镇痛芬太尼和非处方自然抗抑郁剂-ST之间是否存在显着相互作用。约翰的麦芽汁（SJW）在健康志愿者中提取。我们将研究SJW预处理是否会减少静脉内给予芬太尼向大脑的递送，并通过上调P-糖蛋白介导的血脑屏障中的P-糖蛋白介导的外排运输来损害其镇痛功效。受试者将随机分配给两个治疗组之一：安慰剂和主动SJW。对于每个手臂，受试者将在安慰剂或SJW治疗至少14天后的两个单独的研究中接受静脉注射芬太尼。在第一个学习当天，固定剂量的芬太尼将在30分钟内静脉注射。芬太尼的访问率和中枢神经系统可用性将通过遵循阿片类药物对瞳孔大小随时间的影响进行评估。在第二个学习日，将通过计算机控制的泵注入芬太尼，以实现和维持目标稳态血浆芬太尼浓度四个小时。在稳态芬太尼输注期间，将评估阿片类药物的镇痛和副作用。这项研究的结果应指导芬太尼用于麻醉或疼痛管理的临床使用，以治疗抑郁症的患者。