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

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。本研究方案的总体目标是调查广泛使用的阿片类镇痛药芬太尼与非处方天然抗抑郁药st。John's wort （SJW）提取物在健康志愿者中的应用。我们将研究SJW预处理是否会通过上调p糖蛋白介导的血脑屏障外排转运而减少静脉给药芬太尼到脑的输送，并损害其镇痛效果。受试者将被随机分配到两个治疗组中的一个：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天接受静脉注射芬太尼。在第一个研究日，固定剂量的芬太尼将静脉注射超过30分钟。随着时间的推移，阿片类药物对瞳孔大小的影响将评估芬太尼的获取率和中枢神经系统的可用性。在第二天的研究中，芬太尼将通过计算机控制的泵注入，以达到并维持目标稳态血浆芬太尼浓度4小时。在芬太尼稳态输注期间，评估阿片类药物的镇痛和副作用。本研究的结果应该指导芬太尼在服用SJW治疗抑郁症的患者中用于麻醉或疼痛管理的临床应用。

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.