Assessing Goldenseal-drug Interactions Using a Probe Drug Cocktail Approach

• Status: Completed
• Trial end date: 2019-03-31
• Target enrollment: 0
• Participant gender: All

Summary

Goldenseal is a botanical natural product commonly used to self-treat symptoms of the common cold and many digestive disorders. Goldenseal products typically contain the isoquinoline alkaloids berberine, hydrastine, and hydrastinine. These constituents contain a methylenedioxyphenyl ring, a 'structural alert' that can lead to irreversible inhibition of drug metabolizing enzymes, particularly the cytochromes P450 (CYPs). Clinical studies involving healthy volunteers demonstrated that, compared to baseline (absence of goldenseal), CYP2D6 and CYP3A activities were reduced by 40-60% following treatment with goldenseal. Compared to the CYPs, the effects of goldenseal products on drug transporters are understudied, particularly in human subjects. Using a 'cocktail' consisting of 'probe' drug substrates for CYP3A and various transporters, the effects of goldenseal on the pharmacokinetics of each probe drug will be examined in healthy volunteers. Results will provide useful information about the risk of co-consuming goldenseal with additional drugs that are substrates for transporters.

• Phase: Early Phase 1
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: Washington State University
• Collaborator: National Center for Complementary and Integrative Health (NCCIH)
• Treatments: Furosemide; Metformin; Midazolam; Pharmaceutical Solutions; Rosuvastatin Calcium

Criteria

Inclusion Criteria:

• Ability to participate in the study (time, transportation, etc.)

• Ability to understand the informed consent form

• Men and women aged from 18 to 65 years

• Willingness to abstain from alcohol and caffeinated beverages for the evening prior to and during each in-patient study day

• Willingness to abstain from citrus juices and other dietary supplements for the duration of the study

Exclusion Criteria:

• Any current major illness or chronic illness including but not limited to kidney disease, hepatic disease, diabetes mellitus, hypertension, coronary artery disease, chronic obstructive pulmonary disease, previous stroke or embolic disease history, cancer, and HIV/AIDS

• History of allergy to goldenseal, midazolam, furosemide, metformin, or rosuvastatin

• History of anemia or any other significant hematologic disorder

• History of renal failure or lactic acidosis (metformin)

• History of apnea (midazolam)

• History of heart failure, electrolyte imbalance (furosemide)

• History of hypotension (goldenseal)

• History of drug or alcohol addiction or major psychiatric illness

• Women who are intending to become pregnant within the next three months, are currently pregnant, or are currently breastfeeding

• Out-of-range clinical laboratory value that the study physician considers participation in the study a health risk

• Taking concomitant medications, both prescription and non-prescription (including herbal/natural products) known to alter the pharmacokinetics or pharmacodynamics of midazolam, furosemide, metformin, or rosuvastatin.