In Part 1, subjects will be administered thiamine, thiamine with metformin, and thiamine with trimethoprim. Part 2 will expand on Part 1 and subjects will be administered thiamine and thiamine with trimethoprim. The goal is to determine whether taking a drug and a vitamin together affects the body's ability to absorb, distribute, and eliminate thiamine (Vitamin B1).
Thiamine is an essential vitamin meaning humans must consume thiamine from their diet in order to stay healthy. Low thiamine levels can lead to adverse events. Thiamine is absorbed in the intestine by a transporter protein. This is made by the SLC19A3 gene. The SLC19A3 gene provides instructions for making the thiamine transporter protein, which moves thiamine into cells. Certain drugs, like metformin and trimethoprim, have been shown to interrupt function of the SLC19A3 gene. Metformin is a first-line therapy for patients with Type 2 diabetes and is associated with improvements in diabetic complications. Trimethoprim is an anti-bacterial drug that is often prescribed to treat infections such as urinary tract infections. At different phases of this study, participants will be administered thiamine, thiamine with metformin, and/or thiamine with trimethoprim to determine whether taking a drug and a vitamin together affects the body's ability to absorb, distribute, and eliminate thiamine. The levels of thiamine in the participants' blood and urine will be measured before and after taking thiamine or thiamine in combination with metformin and/or trimethoprim.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
NONE
Enrollment
7
300mg of trimethoprim will be given in combination with 5mg thiamine and compared to 5mg thiamine only for both Parts 1 and 2 of the study.
1000mg of metformin will be given in combination with 5mg thiamine and compared to 5mg thiamine only in Part 1 of the study.
5mg of thiamine will be given alone and in combination for both Parts 1 and 2 of the study.
Jean Mayer USDA Human Nutrition Research Center on Aging
Boston, Massachusetts, United States
Maximum Concentration (Cmax) of Thiamine in Plasma Between the Combination Arm(s) and Single Agent Arm
Plasma samples were collected at pre-dose and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 10, 12, and 24 hours post-dose for each cycle. Cmax is determined by taking blood samples at various time points after drug administration and analyzing the thiamine concentration in plasma.
Time frame: The highest concentration of a thiamine observed in the blood plasma after drug administration
Area Under the Curve From 0 to 24 (AUC0-24)Hours of Thiamine in Plasma Between the Combination Arm(s) and Single Agent Arm
Plasma samples were collected at pre-dose and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 10, 12, and 24 hours post-dose for each cycle. AUC0-24 (Area Under the Curve from 0 to 24 hours) is a pharmacokinetic (PK) parameter that represents the total drug exposure in the body over a 24-hour period. It is calculated as the area under the plasma thiamine concentration vs. time curve (from time zero to 24 hours after drug administration).
Time frame: Plasma samples were collected at pre-dose and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 10, 12, and 24 hours post-dose for each cycle.
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