Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
This is an open-label, fixed sequence study of the effect of probiotics supplementation on drug, vitamin, and hormone metabolism.
The investigators hypothesize that probiotic treatment (Visbiome) will alter the activities of major classes of drug metabolizing enzymes. Twelve healthy male subjects will participate in a pharmacokinetic study prior to and following supplementation with Visbiome probiotics for 28 days.
The investigators will determine the pharmacokinetics of oral and intravenous midazolam [metabolized by cytochrome P450 3A enzymes, uridine 5'-diphospho-glucuronosyltransferases (UGTs) and sulfotransferase (SULTs)] and acetaminophen (metabolized by UGTs and SULTs), and the circulating concentrations of endogenous compounds (i.e., testosterone and vitamin D metabolites) prior to and following supplementation with Visbiome probiotics for 28 days. In addition, the investigators will compare the fecal microbiota composition and plasma lipidomic and metabolomics profiles to assess the impact of Visbiome supplementation.
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Probiotics treatment on midazolam and acetaminophen metabolism | Experimental | Experimental: Day 1: midazolam (2 mg oral) + acetaminophen (500 mg oral) + midazolam (1 mg IV) Days 1-28: Visbiome (2 capsules) administered BID Day 11: midazolam (2 mg oral) + acetaminophen (500 mg oral) + midazolam (1 mg IV) |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Visbiome | Dietary Supplement | 2 capsules of Visbiome, a probiotics supplement, twice a day (morning and evening) for 28 days |
|
| Measure | Description | Time Frame |
|---|---|---|
| Oral midazolam peak concentration (Cmax) | Following 2 mg midazolam syrup given orally at time = 0 | 0 to 3 hours on Days 1 and 29 |
| IV midazolam peak concentration (Cmax) | Following 1 mg midazolam given IV at time = 3 hrs | 3 to 12 hours on Days 1 and 29 |
| Overall midazolam area under the curve (AUC) | Following 2 mg midazolam syrup given orally and 1 mg midazolam given IV | 0 to 12 hours on Days 1 and 29 |
| Overall 1'-hydroxymidazolam area under the curve (AUC) | Following 2 mg midazolam syrup given orally and 1 mg midazolam given IV | 0 to 12 hours on Days 1 and 29 |
| Acetaminophen peak concentration (Cmax) | 500 mg acetaminophen given orally | 0 to 12 hours on Days 1 and 29 |
| Acetaminophen area under the curve (AUC) | 500 mg acetaminophen given orally at time = 0 | 0 to 12 hours on Days 1 and 29 |
| Acetaminophen-glucuronide area under the curve (AUC) | 500 mg acetaminophen given orally at time = 0 | 0 to 12 hours on Days 1 and 29 |
| Acetaminophen-sulfate area under the curve (AUC) |
| Measure | Description | Time Frame |
|---|---|---|
| Midazolam terminal half-life | Following 2 mg midazolam syrup given orally and 1 mg midazolam given IV | 0 to 12 hours on Days 1 and 29 |
| Acetaminophen terminal half-life | 500 mg acetaminophen given orally at time = 0 |
| Measure | Description | Time Frame |
|---|---|---|
| Microbiome composition of fecal sample | Compositional studies using sequencing of 16S gene | Days 1 and 29 |
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Yvonne Lin, PhD | Contact | 206-616-8728 | yvonlin@uw.edu |
| Name | Affiliation | Role |
|---|---|---|
| Yvonne Lin, PhD | University of Washington | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Washington | Recruiting | Seattle | Washington | 98195 | United States |
Not provided
Single arm prospective study
Not provided
Not provided
Not provided
Not provided
500 mg acetaminophen given orally at time = 0
| 0 to 12 hours on Days 1 and 29 |
| 0 to 12 hours on Days 1 and 29 |
| Urinary excretion of 1'-hydroxymidazolam | Amount of 1'-hydroxymidazolam recovered in urine | 0 to 12 hours on Days 1 and 29 |
| Urinary excretion of acetaminophen-glucuronide | Amount of acetaminophen-glucuronide recovered in urine | 0 to 12 hours on Days 1 and 29 |
| Urinary excretion of acetaminophen-sulfate | Amount of acetaminophen-sulfate recovered in urine | 0 to 12 hours on Days 1 and 29 |