Licorice Botanical Dietary Supplements - Metabolism and Safety in Women

University of Illinois

Status and phase

Completed

Phase 1

Conditions

Food-drug Interaction

Treatments

Drug: Caffeine 100 MG

Drug: Dextromethorphan 30mg

Dietary Supplement: Licorice

Drug: Tolbutamide 250 mg

Drug: Alprazolam 2 MG

Study type

Interventional

Funder types

Other

Identifiers

NCT03948243

2019-0115

Details and patient eligibility

About

Human safety studies will be carried out to test whether red clover botanical dietary supplements used by peri- and post-menopausal women are safe to use with Food and Drug Administration (FDA)-approved drugs. To test this, a red clover dietary supplement (previously tested in women at the University of Illinois at Chicago without any harmful effects) will be given with four selected FDA-approved drugs to determine if the Licorice supplement can increase or decrease how these medications are absorbed, metabolized and excreted by the human body. Preclinical studies predict that the licorice supplement might affect the metabolism or break down of these probe drugs.

Full description

At the start of a study, subjects will be administered low doses of a mixture of four FDA-approved drugs (caffeine, tolbutamide, dextromethorphan, and alprazolam), and serial blood samples will be drawn and analyzed for the concentration of each drug over time. Afterwards, participants will take the licorice dietary supplement twice daily for 14 days to allow for potential inhibition or induction of drug metabolizing enzymes and transporters. Thereafter, the same drugs will be taken again to obtain a second measure of drug concentrations in blood over time. Changes in the concentration-time curve values for each probe drug obtained before and after ingestion of the supplement would indicate that metabolism of the probe drugs is impacted by the licorice dietary supplement.

Enrollment

19 patients

Sex

Female

Ages

40 to 79 years old

Volunteers

Accepts Healthy Volunteers

Inclusion criteria

healthy peri- and post-menopausal women ages 40 - 79
non-smokers
no-significant medical conditions as assessed by subject-reported medical history, physical examination and blood and urine chemistry screens
no medical condition that requires chronic use of medication

Exclusion criteria

known allergies or hypersensitivity to caffeine, dextromethorphan, sulfonylureas (tolbutamide), benzodiazepines, or licorice
positive pregnancy test
use of hormone therapy within 8 weeks of study initiation for oral agents, 4 weeks for transdermal or other topical agents
use of caffeine products 7 days before study participation or during the study
use of citrus products 7 days before study participation or during the study
other prescription (with the exception of the Mirena® IUD) or non-prescription medicines within the 2 weeks prior to study initiation or during the study
chronic diseases, such as inflammatory bowel disease, that could alter the absorption or metabolism of the probe substrates
unwillingness to comply with study requirements
current participation in another clinical trial
CYP2D6 deficiency based on phenotyping at screening
smoker
licorice (whether as a botanical dietary supplement, candy, food, drink or otherwise) within the previous two weeks and during the study
use of any dietary supplements within the last 2 weeks prior to study initiation and during the study
extreme obesity (defined as >40 BMI)
alcohol or drug abuse
chronic diseases such as diabetes.