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

点击翻译按钮获取中文摘要

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.