Ignite Creation Date:
2024-05-05 @ 11:24 AM
Last Modification Date:
2024-10-26 @ 9:06 AM
Study NCT ID:
NCT00027014
Status:
COMPLETED
Last Update Posted:
2007-02-08
First Post:
2001-11-15
Brief Title:
Herb-Opioid Interactions
Sponsor:
National Center for Complementary and Integrative Health NCCIH
Organization:
National Center for Complementary and Integrative Health NCCIH
Study Overview
Official Title:
Herb-Opioid Interactions
Status:
COMPLETED
Status Verified Date:
2006-07
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This is a series of studies in healthy volunteers to assess the potential for adverse interactions between St Johns wort SJW extract and two narcotic opioid pain medications oxycodone and fentanyl In the case of oxycodone we are interested in whether SJW treatment promotes the metabolism of oxycodone such that it lowers the effectiveness of standard doses of oxycodone in treating pain problems For the fentanyl study we will investigate whether SJW treatment will interfere with the delivery of fentanyl to the brain and diminish its effectiveness to relieve pain There is evidence to suggest that SJW treatment may increase the activity of a transporter protein named P-glycoprotein Pgp in the blood-brain barrier BBB that protects the brain from exposure to drugs and other dietary and environmental toxins
Detailed Description:
Extract of St Johns wort SJW Hypericum perforatum has gained widespread popularity as an over-the-counter natural antidepressant Until recently SJW was thought to be well tolerated and relatively safe Within the past year adverse metabolic interactions have been reported between SJW and several narrow therapeutic index drugs notably cyclosporine indinavir and digoxin The interactions are now recognized to involve induction of two drug disposition mechanisms cytochrome P450 3A4 enzyme and the active efflux pump P-glycoprotein both leading to profound reductions in blood or plasma drug concentration that compromises the therapeutic efficacy of the affected drug Natural and synthetic opioids are the first-line agents for the palliative treatment of severe pain that results from cancer and cancer treatment It is well recognized that depression is a co-morbid condition of severe and poorly controlled cancer-related pain Given the widespread recognition of St Johns wort as a mood enhancer and natural antidepressant cancer pain patients receiving opioid analgesics may well turn to this herbal preparation for relief of depressive symptoms
The overall objective of this research proposal is to investigate if significant interactions occur between two widely used opioid analgesics -- oxycodone and fentanyl and St John wort extract through laboratory-based studies in healthy volunteers The studies will assess the potential clinical significance of the interactions with respect to opioid analgesia efficacy and side effects and provide scientific insights into the pharmacokinetic mechanisms underlying any observed interactions
The oxycodone arm of the study is designed to 1 investigate the induction of CYP3A4-mediated N-demethylation which is the major detoxification pathway for oxycodone and 2 resolve the inductive effects of SJW on intestinal and hepatic CYP3A4 through intravenous and oral administrations of a CYP3A-specific in vivo catalytic probe -midazolam
The fentanyl arm of the study is designed to 1 assess the effects of SJW on the brain uptake and efflux kinetics of fentanyl through pharmacokinetic-pharmacodynamic PK-PD modeling of miotic response over time during and following intravenous infusion of the opioid and 2 To evaluate the changes in analgesia and side effects of fentanyl upon pretreatment with SJW that may have resulted from induction of Pgp at the BBB
Overall the proposed research will provide a definitive assessment of the potential and clinical significance of adverse interactions between SJW and opioids in the context of cancer pain therapy
The overall objective of this research proposal is to investigate if significant interactions occur between two widely used opioid analgesics -- oxycodone and fentanyl and St John wort extract through laboratory-based studies in healthy volunteers The studies will assess the potential clinical significance of the interactions with respect to opioid analgesia efficacy and side effects and provide scientific insights into the pharmacokinetic mechanisms underlying any observed interactions
The oxycodone arm of the study is designed to 1 investigate the induction of CYP3A4-mediated N-demethylation which is the major detoxification pathway for oxycodone and 2 resolve the inductive effects of SJW on intestinal and hepatic CYP3A4 through intravenous and oral administrations of a CYP3A-specific in vivo catalytic probe -midazolam
The fentanyl arm of the study is designed to 1 assess the effects of SJW on the brain uptake and efflux kinetics of fentanyl through pharmacokinetic-pharmacodynamic PK-PD modeling of miotic response over time during and following intravenous infusion of the opioid and 2 To evaluate the changes in analgesia and side effects of fentanyl upon pretreatment with SJW that may have resulted from induction of Pgp at the BBB
Overall the proposed research will provide a definitive assessment of the potential and clinical significance of adverse interactions between SJW and opioids in the context of cancer pain therapy
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None