Bile Salt Export Pump (BSEP) Transporter, Polysorbate 80
Conditions
Keywords
healthy volunteer, pharmacokinetics, excipient, transporter
Brief summary
The study employs two-sub-studies that share a common placebo arm. The objective of one sub-study is to assess the impact of metformin on pravastatin and chenodeoxycholic acid pharmacokinetics. We hypothesize that metformin represses the bile salt export pump (BSEP) in the liver, which excretes pravastatin and chenodeoxycholic acid from the liver into the bile. The objective of the other sub-study is to assess the impact of polysorbate 80 on valacyclovir, chenodeoxycholic acid, and enalaprilat pharmacokinetics. We hypothesize that polysorbate 80 inhibits uptake transporters in the intestine, which absorb valacyclovir and chenodeoxycholic acid in the gut via the peptide transporter 1 (PepT1) and apical sodium-bile acid transporter (ASBT), respectively. Enalaprilat is passively absorbed but with low permeability, and thus serves as a passive absorption reference.
Interventions
DRUGpravastatin and chenodeoxycholic acid, after metformin and placebo
single oral dose of pravastatin 80 mg and chenodeoxycholic acid 250 mg
DRUGvalacyclovir, chenodeoxycholic acid, and enalaprilat, after polysorbate 80 and placebo
single oral dose of valacyclovir 500 mg, chenodeoxycholic acid 250 mg, and enalaprilat 20 mg
Sponsors
University of Maryland, Baltimore
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
* Subject is healthy, as determined by screening evaluation that is not greater than 60 days before the first study visit. * Subject is male or female between 18 and 65 years of age, inclusive. * Subject is an acceptable candidate for venipuncture. * Subject is willing to stop all non-routine OTC medications, as well as vitamins, dietary supplements, and herbals, for 24 hours prior to study drug administration and during pharmacokinetic study visits.
Exclusion criteria
* Subject has a significant medical disease (including cardiovascular, pulmonary, hematologic, endocrine, immunologic, neurologic, renal, gastrointestinal, metabolic, or psychiatric). * Subject has a clinically significant history or presence of any clinically significant gastrointestinal pathology (e.g. chronic diarrhea, inflammatory bowel diseases), unresolved gastrointestinal symptoms (e.g. diarrhea, vomiting), liver or kidney disease, or other conditions known to interfere with the absorption, distribution, metabolism or excretion of study drugs. * Subject has a history of liver or gallbladder disease, or history of myopathy * Subject has a history of angioedema either with or without previous treatment with an angiotensin converting enzyme inhibitor. * Subject was previously diagnosed with diabetes, or treated with antidiabetic agents * Subject has a history of alcohol or drug abuse, which in the opinion of the PI or medical physician, could jeopardize the subject's health or would compromise the subject's ability to participate in this trial. * Subject is pregnant, breast feeding, or trying to become pregnant. * Female subject of childbearing potential is unwilling or unable to use a medically acceptable method of contraception throughout the entire study period and for one week after the study is completed. Medically acceptable methods of contraception that may be used by the subject and/or her partner are: oral birth control pill, condom with spermicide, diaphragm with spermicide, IUD, vaginal spermicidal suppository, surgical sterilization of patient or their partner(s), abstinence, or hormonal-based patches, ring, injections, and implants. * Subject routinely uses (i.e. daily or weekly) prescription medication except hormonal birth control medication, routinely uses (i.e. daily or weekly) OTC medication, or routinely uses niacin to treat hypercholesterolemia. OTC medications do not include vitamins, dietary supplements, or herbals. * Subject routinely uses (i.e. daily or weekly) acid blockers, antacids, anti-diarrhea, stimulants, appetite suppressants, or anti-nausea medication or other drugs that modulate GI function. * Subject is currently taking metformin, valacyclovir, acyclovir, chenodiol, pravastatin, enalapril, enalaprilat, or medications known to interact with any of these medications. * Subject has a history or allergy or sensitivity to metformin, valacyclovir, acyclovir, chenodiol, pravastatin, polysorbate 80, enalapril, enalaprilat, or history of any drug hypersensitivity or intolerance which, in the opinion of the PI or medical physician, would compromise the safety of the subject or the study. * Subject has liver impairment as assessed by alanine aminotransferase (ALT), aspartate aminotransferase (AST), or total bilirubin levels greater than the upper limit of normal (ULN). * Subject has renal impairment as assessed by creatinine clearance lower than 60mL/min/1.73m2, using the CKDEPI formula. * Subject is not willing or able to be adherent to study protocol (e.g., study visits). * Subject has a condition in which in the opinion of the PI or medical physician would increase risk to the subject or interfere with the integrity of the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Peak Plasma Concentration (Cmax) of Enalaprilat After Polysorbate 80 | 0-10 hours | Enalaprilat Cmax after polysorbate 80. Cmax units are concentration (i.e. ng/ml). |
| Peak Plasma Concentration (Cmax) of Acyclovir After Polysorbate 80 | 0-10 hours | Acyclovir Cmax after polysorbate 80. Cmax units are concentration (i.e. ng/ml). |
| Area-Under-the-Curve (AUC) of Chenodeoxycholic Acid (CDCA) After Polysorbate 80 | 0-10 hours | Baseline-corrected Chenodeoxycholic acid AUC after polysorbate 80. AUC units are concentration x time (i.e. ng/ml x h). Baseline-corrected chenodeoxycholic acid is chenodeoxycholic acid concentration minus chenodeoxycholic acid concentration value at time zero (i.e. t=0). |
| Peak Plasma Concentration (Cmax) of Chenodeoxycholic Acid (CDCA) After Polysorbate 80 | 0-10 hours | Baseline-corrected Chenodeoxycholic acid Cmax after polysorbate 80. Cmax units are concentration (i.e. ng/ml). Baseline-corrected chenodeoxycholic acid is chenodeoxycholic acid concentration minus chenodeoxycholic acid concentration value at time zero (i.e. t=0). |
| Area-Under-the-Curve (AUC) of Enalaprilat After Polysorbate 80 | 0-10 hours | Enalaprilat AUC after polysorbate 80. AUC units are concentration x time (i.e. ng/ml x h). |
| Area-Under-the-Curve (AUC) of Pravastatin After Metformin | 0-10 hours | Pravastatin AUC after metformin, compared to pravastatin AUC after placebo. AUC units are concentration x time (i.e. ng/ml x h). |
| Peak Plasma Concentration (Cmax) of Pravastatin After Metformin | 0-10 hours | Pravastatin Cmax after metformin, compared to pravastatin Cmax after placebo. Cmax units are concentration (i.e. ng/ml). |
| Area-Under-the-Curve (AUC) of Chenodeoxycholic Acid After Metformin | 0-10 hours | Baseline-corrected chenodeoxycholic acid AUC after metformin. AUC Units are concentration x time (i.e. ng/ml x h). Baseline-corrected chenodeoxycholic acid is chenodeoxycholic acid concentration minus chenodeoxycholic acid concentration value at time zero (i.e. t=0). |
| Peak Plasma Concentration (Cmax) of Chenodeoxycholic Acid After Metformin | 0-10 hours | Baseline-corrected chenodeoxycholic acid Cmax after metformin. Cmax units are concentration (i.e. ng/ml). Baseline-corrected chenodeoxycholic acid is chenodeoxycholic acid concentration minus chenodeoxycholic acid concentration value at time zero (i.e. t=0). |
| Area-Under-the-Curve (AUC) of Acyclovir After Polysorbate 80 | 0-10 hours | Acyclovir AUC after polysorbate 80. AUC units are concentration x time (i.e. ng/ml x h). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Peak Plasma Concentration (Cmax) of Endogenous Bile Acids After Metformin | 0-10 hours | For each of 15 endogenous bile acid, endogenous bile acid Cmax after metformin, compared to endogenous bile acid Cmax after placebo. Cmax units are concentration (i.e. ng/ml). |
| Area-Under-the-Curve (AUC) of Endogenous Bile Acids After Metformin | 0-10 hours | For each of 15 endogenous bile acid, endogenous bile acid AUC after metformin, compared to endogenous bile acid AUC after placebo. AUC units are concentration x time (i.e. ng/ml x h). |
| Peak Plasma Concentration (Cmax) of Endogenous Bile Acids After Polysorbate 80 | 0-10 hours | For each of 15 endogenous bile acid, endogenous bile acid Cmax after polysorbate 80, compared to endogenous bile acid Cmax after placebo. Cmax units are concentration (i.e. ng/ml). |
| Area-Under-the-Curve (AUC) of Endogenous Bile Acids After Polysorbate 80 | 0-10 hours | For each of 15 endogenous bile acid, endogenous bile acid AUC after polysorbate 80, compared to endogenous bile acid AUC after placebo. AUC units are concentration x time (i.e. ng/ml x h). |
Countries
United States
Participant flow
Pre-assignment details
UMB IRB, a subject is enrolled if they signed a consent form, regardless if they passed screening.
Participants by arm
| Arm | Count |
|---|---|
| Placebo, Then Metformin, Then Polysorbate 80 Placebo is one twice a day, metformin is 500mg twice a day, and polysorbate 80 is 400mg twice a day
pravastatin and chenodeoxycholic acid, after metformin and placebo: single oral dose of pravastatin 80 mg and chenodeoxycholic acid 250 mg
valacyclovir, chenodeoxycholic acid, and enalaprilat, after polysorbate 80 and placebo: single oral dose of valacyclovir 500 mg, chenodeoxycholic acid 250 mg, and enalaprilat 20 mg | 2 |
| Metformin, Then Polysorbate 80, Then Placebo Placebo is one twice a day, metformin is 500mg twice a day, and polysorbate 80 is 400mg twice a day
pravastatin and chenodeoxycholic acid, after metformin and placebo: single oral dose of pravastatin 80 mg and chenodeoxycholic acid 250 mg
valacyclovir, chenodeoxycholic acid, and enalaprilat, after polysorbate 80 and placebo: single oral dose of valacyclovir 500 mg, chenodeoxycholic acid 250 mg, and enalaprilat 20 mg | 2 |
| Polysorbate 80, Then Placebo, Then Metformin Placebo is one twice a day, metformin is 500mg twice a day, and polysorbate 80 is 400mg twice a day
pravastatin and chenodeoxycholic acid, after metformin and placebo: single oral dose of pravastatin 80 mg and chenodeoxycholic acid 250 mg
valacyclovir, chenodeoxycholic acid, and enalaprilat, after polysorbate 80 and placebo: single oral dose of valacyclovir 500 mg, chenodeoxycholic acid 250 mg, and enalaprilat 20 mg | 2 |
| Polysorbate 80, Then Metformin, Then Placebo Placebo is one twice a day, metformin is 500mg twice a day, and polysorbate 80 is 400mg twice a day
pravastatin and chenodeoxycholic acid, after metformin and placebo: single oral dose of pravastatin 80 mg and chenodeoxycholic acid 250 mg
valacyclovir, chenodeoxycholic acid, and enalaprilat, after polysorbate 80 and placebo: single oral dose of valacyclovir 500 mg, chenodeoxycholic acid 250 mg, and enalaprilat 20 mg | 2 |
| Placebo, Then Polysorbate 80, Then Metformin Placebo is one twice a day, metformin is 500mg twice a day, and polysorbate 80 is 400mg twice a day
pravastatin and chenodeoxycholic acid, after metformin and placebo: single oral dose of pravastatin 80 mg and chenodeoxycholic acid 250 mg
valacyclovir, chenodeoxycholic acid, and enalaprilat, after polysorbate 80 and placebo: single oral dose of valacyclovir 500 mg, chenodeoxycholic acid 250 mg, and enalaprilat 20 mg | 2 |
| Metformin, Then Placebo, Then Polysorbate 80 Placebo is one twice a day, metformin is 500mg twice a day, and polysorbate 80 is 400mg twice a day
pravastatin and chenodeoxycholic acid, after metformin and placebo: single oral dose of pravastatin 80 mg and chenodeoxycholic acid 250 mg
valacyclovir, chenodeoxycholic acid, and enalaprilat, after polysorbate 80 and placebo: single oral dose of valacyclovir 500 mg, chenodeoxycholic acid 250 mg, and enalaprilat 20 mg | 2 |
| Total | 12 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Overall Study | Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 2 |
Baseline characteristics
| Characteristic | Metformin, Then Polysorbate 80, Then Placebo | Polysorbate 80, Then Placebo, Then Metformin | Polysorbate 80, Then Metformin, Then Placebo | Placebo, Then Metformin, Then Polysorbate 80 | Placebo, Then Polysorbate 80, Then Metformin | Metformin, Then Placebo, Then Polysorbate 80 | Total |
|---|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 2 Participants | 2 Participants | 2 Participants | 2 Participants | 2 Participants | 2 Participants | 12 Participants |
| Age, Continuous | 26.5 years | 28.5 years | 26.5 years | 28.5 years | 40 years | 28 years | 29.7 years |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized Black/African American | 0 Participants | 1 Participants | 2 Participants | 0 Participants | 1 Participants | 2 Participants | 6 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized White/Caucasian | 1 Participants | 0 Participants | 0 Participants | 2 Participants | 1 Participants | 0 Participants | 4 Participants |
| Region of Enrollment United States | 2 Participants | 2 Participants | 2 Participants | 2 Participants | 2 Participants | 2 Participants | 12 Participants |
| Sex: Female, Male Female | 2 Participants | 0 Participants | 1 Participants | 2 Participants | 1 Participants | 1 Participants | 7 Participants |
| Sex: Female, Male Male | 0 Participants | 2 Participants | 1 Participants | 0 Participants | 1 Participants | 1 Participants | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 13 | 0 / 12 | 0 / 13 |
| other Total, other adverse events | 8 / 13 | 2 / 12 | 4 / 13 |
| serious Total, serious adverse events | 0 / 13 | 0 / 12 | 0 / 13 |
Outcome results
Primary
Area-Under-the-Curve (AUC) of Acyclovir After Polysorbate 80
Acyclovir AUC after polysorbate 80. AUC units are concentration x time (i.e. ng/ml x h).
Time frame: 0-10 hours
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Metformin | Area-Under-the-Curve (AUC) of Acyclovir After Polysorbate 80 | 10039 ng/ml x h | Standard Error 903 |
| Placebo | Area-Under-the-Curve (AUC) of Acyclovir After Polysorbate 80 | 9839 ng/ml x h | Standard Error 782 |
p-value: <0.05t-test, 1 sided
Primary
Area-Under-the-Curve (AUC) of Chenodeoxycholic Acid After Metformin
Baseline-corrected chenodeoxycholic acid AUC after metformin. AUC Units are concentration x time (i.e. ng/ml x h). Baseline-corrected chenodeoxycholic acid is chenodeoxycholic acid concentration minus chenodeoxycholic acid concentration value at time zero (i.e. t=0).
Time frame: 0-10 hours
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Metformin | Area-Under-the-Curve (AUC) of Chenodeoxycholic Acid After Metformin | 4646 ng/ml x h | Standard Error 352 |
| Placebo | Area-Under-the-Curve (AUC) of Chenodeoxycholic Acid After Metformin | 4665 ng/ml x h | Standard Error 370 |
p-value: <0.05t-test, 1 sided
Primary
Area-Under-the-Curve (AUC) of Chenodeoxycholic Acid (CDCA) After Polysorbate 80
Baseline-corrected Chenodeoxycholic acid AUC after polysorbate 80. AUC units are concentration x time (i.e. ng/ml x h). Baseline-corrected chenodeoxycholic acid is chenodeoxycholic acid concentration minus chenodeoxycholic acid concentration value at time zero (i.e. t=0).
Time frame: 0-10 hours
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Metformin | Area-Under-the-Curve (AUC) of Chenodeoxycholic Acid (CDCA) After Polysorbate 80 | 4964 ng/ml x h | Standard Error 300 |
| Placebo | Area-Under-the-Curve (AUC) of Chenodeoxycholic Acid (CDCA) After Polysorbate 80 | 4665 ng/ml x h | Standard Error 370 |
p-value: <0.05t-test, 1 sided
Primary
Area-Under-the-Curve (AUC) of Enalaprilat After Polysorbate 80
Enalaprilat AUC after polysorbate 80. AUC units are concentration x time (i.e. ng/ml x h).
Time frame: 0-10 hours
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Metformin | Area-Under-the-Curve (AUC) of Enalaprilat After Polysorbate 80 | 10.98 ng/ml x h | Standard Error 3.05 |
| Placebo | Area-Under-the-Curve (AUC) of Enalaprilat After Polysorbate 80 | 12.10 ng/ml x h | Standard Error 2.71 |
p-value: <0.05t-test, 1 sided
Primary
Area-Under-the-Curve (AUC) of Pravastatin After Metformin
Pravastatin AUC after metformin, compared to pravastatin AUC after placebo. AUC units are concentration x time (i.e. ng/ml x h).
Time frame: 0-10 hours
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Metformin | Area-Under-the-Curve (AUC) of Pravastatin After Metformin | 264.2 ng/ml × h | Standard Error 34.1 |
| Placebo | Area-Under-the-Curve (AUC) of Pravastatin After Metformin | 170.5 ng/ml × h | Standard Error 24.7 |
p-value: 0.02t-test, 1 sided
Primary
Peak Plasma Concentration (Cmax) of Acyclovir After Polysorbate 80
Acyclovir Cmax after polysorbate 80. Cmax units are concentration (i.e. ng/ml).
Time frame: 0-10 hours
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Metformin | Peak Plasma Concentration (Cmax) of Acyclovir After Polysorbate 80 | 3363 ng/ml | Standard Error 348 |
| Placebo | Peak Plasma Concentration (Cmax) of Acyclovir After Polysorbate 80 | 3230 ng/ml | Standard Error 367 |
p-value: <0.05t-test, 1 sided
Primary
Peak Plasma Concentration (Cmax) of Chenodeoxycholic Acid After Metformin
Baseline-corrected chenodeoxycholic acid Cmax after metformin. Cmax units are concentration (i.e. ng/ml). Baseline-corrected chenodeoxycholic acid is chenodeoxycholic acid concentration minus chenodeoxycholic acid concentration value at time zero (i.e. t=0).
Time frame: 0-10 hours
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Metformin | Peak Plasma Concentration (Cmax) of Chenodeoxycholic Acid After Metformin | 2695 ng/ml | Standard Error 453 |
| Placebo | Peak Plasma Concentration (Cmax) of Chenodeoxycholic Acid After Metformin | 2881 ng/ml | Standard Error 351 |
p-value: <0.05t-test, 1 sided
Primary
Peak Plasma Concentration (Cmax) of Chenodeoxycholic Acid (CDCA) After Polysorbate 80
Baseline-corrected Chenodeoxycholic acid Cmax after polysorbate 80. Cmax units are concentration (i.e. ng/ml). Baseline-corrected chenodeoxycholic acid is chenodeoxycholic acid concentration minus chenodeoxycholic acid concentration value at time zero (i.e. t=0).
Time frame: 0-10 hours
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Metformin | Peak Plasma Concentration (Cmax) of Chenodeoxycholic Acid (CDCA) After Polysorbate 80 | 2960 ng/ml | Standard Error 276 |
| Placebo | Peak Plasma Concentration (Cmax) of Chenodeoxycholic Acid (CDCA) After Polysorbate 80 | 2881 ng/ml | Standard Error 351 |
p-value: <0.05t-test, 1 sided
Primary
Peak Plasma Concentration (Cmax) of Enalaprilat After Polysorbate 80
Enalaprilat Cmax after polysorbate 80. Cmax units are concentration (i.e. ng/ml).
Time frame: 0-10 hours
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Metformin | Peak Plasma Concentration (Cmax) of Enalaprilat After Polysorbate 80 | 1.720 ng/ml | Standard Error 0.48 |
| Placebo | Peak Plasma Concentration (Cmax) of Enalaprilat After Polysorbate 80 | 2.080 ng/ml | Standard Error 0.54 |
p-value: <0.05t-test, 1 sided
Primary
Peak Plasma Concentration (Cmax) of Pravastatin After Metformin
Pravastatin Cmax after metformin, compared to pravastatin Cmax after placebo. Cmax units are concentration (i.e. ng/ml).
Time frame: 0-10 hours
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Metformin | Peak Plasma Concentration (Cmax) of Pravastatin After Metformin | 119.3 ng/ml | Standard Error 17.7 |
| Placebo | Peak Plasma Concentration (Cmax) of Pravastatin After Metformin | 86.43 ng/ml | Standard Error 15.86 |
p-value: <0.05t-test, 1 sided
Secondary
Area-Under-the-Curve (AUC) of Endogenous Bile Acids After Metformin
For each of 15 endogenous bile acid, endogenous bile acid AUC after metformin, compared to endogenous bile acid AUC after placebo. AUC units are concentration x time (i.e. ng/ml x h).
Time frame: 0-10 hours
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Metformin | Area-Under-the-Curve (AUC) of Endogenous Bile Acids After Metformin | Cholic acid | 212.0 ng/ml x h | Standard Error 46.3 |
| Metformin | Area-Under-the-Curve (AUC) of Endogenous Bile Acids After Metformin | Glycocholic acid | 678.5 ng/ml x h | Standard Error 131.4 |
| Metformin | Area-Under-the-Curve (AUC) of Endogenous Bile Acids After Metformin | Taurocholic acid | 126.5 ng/ml x h | Standard Error 30.2 |
| Metformin | Area-Under-the-Curve (AUC) of Endogenous Bile Acids After Metformin | Deoxycholic acid | 1366 ng/ml x h | Standard Error 314 |
| Metformin | Area-Under-the-Curve (AUC) of Endogenous Bile Acids After Metformin | Glycodeoxycholic acid | 1618 ng/ml x h | Standard Error 269 |
| Metformin | Area-Under-the-Curve (AUC) of Endogenous Bile Acids After Metformin | Taurodeoxycholic acid | 233.3 ng/ml x h | Standard Error 36.9 |
| Metformin | Area-Under-the-Curve (AUC) of Endogenous Bile Acids After Metformin | Chenodeoxycholic acid | 5290 ng/ml x h | Standard Error 353 |
| Metformin | Area-Under-the-Curve (AUC) of Endogenous Bile Acids After Metformin | Glycochenodeoxycholic acid | 6499 ng/ml x h | Standard Error 1122 |
| Metformin | Area-Under-the-Curve (AUC) of Endogenous Bile Acids After Metformin | Taurochenodeoxycholic acid | 879.8 ng/ml x h | Standard Error 132.5 |
| Metformin | Area-Under-the-Curve (AUC) of Endogenous Bile Acids After Metformin | Lithocholic acid | 70.10 ng/ml x h | Standard Error 10.74 |
| Metformin | Area-Under-the-Curve (AUC) of Endogenous Bile Acids After Metformin | Glycolithocholic acid | 164.3 ng/ml x h | Standard Error 30.3 |
| Metformin | Area-Under-the-Curve (AUC) of Endogenous Bile Acids After Metformin | Taurolithocholic acid | 17.39 ng/ml x h | Standard Error 3 |
| Metformin | Area-Under-the-Curve (AUC) of Endogenous Bile Acids After Metformin | Ursodeoxycholic acid | 283.5 ng/ml x h | Standard Error 168.9 |
| Metformin | Area-Under-the-Curve (AUC) of Endogenous Bile Acids After Metformin | Glycoursodeoxycholic acid | 625.9 ng/ml x h | Standard Error 220.8 |
| Metformin | Area-Under-the-Curve (AUC) of Endogenous Bile Acids After Metformin | Tauroursodeoxycholic acid | 15.03 ng/ml x h | Standard Error 3.17 |
| Placebo | Area-Under-the-Curve (AUC) of Endogenous Bile Acids After Metformin | Cholic acid | 259.7 ng/ml x h | Standard Error 64.6 |
| Placebo | Area-Under-the-Curve (AUC) of Endogenous Bile Acids After Metformin | Taurochenodeoxycholic acid | 1393 ng/ml x h | Standard Error 195 |
| Placebo | Area-Under-the-Curve (AUC) of Endogenous Bile Acids After Metformin | Glycocholic acid | 1053 ng/ml x h | Standard Error 187 |
| Placebo | Area-Under-the-Curve (AUC) of Endogenous Bile Acids After Metformin | Ursodeoxycholic acid | 243.7 ng/ml x h | Standard Error 159.7 |
| Placebo | Area-Under-the-Curve (AUC) of Endogenous Bile Acids After Metformin | Taurocholic acid | 248.1 ng/ml x h | Standard Error 39.5 |
| Placebo | Area-Under-the-Curve (AUC) of Endogenous Bile Acids After Metformin | Lithocholic acid | 67.64 ng/ml x h | Standard Error 14.64 |
| Placebo | Area-Under-the-Curve (AUC) of Endogenous Bile Acids After Metformin | Deoxycholic acid | 1222 ng/ml x h | Standard Error 158 |
| Placebo | Area-Under-the-Curve (AUC) of Endogenous Bile Acids After Metformin | Tauroursodeoxycholic acid | 17.07 ng/ml x h | Standard Error 3.33 |
| Placebo | Area-Under-the-Curve (AUC) of Endogenous Bile Acids After Metformin | Glycodeoxycholic acid | 1507 ng/ml x h | Standard Error 200 |
| Placebo | Area-Under-the-Curve (AUC) of Endogenous Bile Acids After Metformin | Glycolithocholic acid | 192.1 ng/ml x h | Standard Error 57.8 |
| Placebo | Area-Under-the-Curve (AUC) of Endogenous Bile Acids After Metformin | Taurodeoxycholic acid | 329.3 ng/ml x h | Standard Error 53.1 |
| Placebo | Area-Under-the-Curve (AUC) of Endogenous Bile Acids After Metformin | Glycoursodeoxycholic acid | 542.1 ng/ml x h | Standard Error 181.9 |
| Placebo | Area-Under-the-Curve (AUC) of Endogenous Bile Acids After Metformin | Chenodeoxycholic acid | 5552 ng/ml x h | Standard Error 471 |
| Placebo | Area-Under-the-Curve (AUC) of Endogenous Bile Acids After Metformin | Taurolithocholic acid | 21.02 ng/ml x h | Standard Error 4.55 |
| Placebo | Area-Under-the-Curve (AUC) of Endogenous Bile Acids After Metformin | Glycochenodeoxycholic acid | 7386 ng/ml x h | Standard Error 847 |
p-value: <0.05t-test, 1 sided
Secondary
Area-Under-the-Curve (AUC) of Endogenous Bile Acids After Polysorbate 80
For each of 15 endogenous bile acid, endogenous bile acid AUC after polysorbate 80, compared to endogenous bile acid AUC after placebo. AUC units are concentration x time (i.e. ng/ml x h).
Time frame: 0-10 hours
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Metformin | Area-Under-the-Curve (AUC) of Endogenous Bile Acids After Polysorbate 80 | Cholic acid | 264.3 ng/ml x h | Standard Error 50.6 |
| Metformin | Area-Under-the-Curve (AUC) of Endogenous Bile Acids After Polysorbate 80 | Glycocholic acid | 1171 ng/ml x h | Standard Error 185 |
| Metformin | Area-Under-the-Curve (AUC) of Endogenous Bile Acids After Polysorbate 80 | Taurocholic acid | 280.8 ng/ml x h | Standard Error 40.9 |
| Metformin | Area-Under-the-Curve (AUC) of Endogenous Bile Acids After Polysorbate 80 | Deoxycholic acid | 1451 ng/ml x h | Standard Error 242 |
| Metformin | Area-Under-the-Curve (AUC) of Endogenous Bile Acids After Polysorbate 80 | Glycodeoxycholic acid | 1655 ng/ml x h | Standard Error 183 |
| Metformin | Area-Under-the-Curve (AUC) of Endogenous Bile Acids After Polysorbate 80 | Taurodeoxycholic acid | 346.7 ng/ml x h | Standard Error 38.6 |
| Metformin | Area-Under-the-Curve (AUC) of Endogenous Bile Acids After Polysorbate 80 | Chenodeoxycholic acid | 5718 ng/ml x h | Standard Error 409 |
| Metformin | Area-Under-the-Curve (AUC) of Endogenous Bile Acids After Polysorbate 80 | Glycochenodeoxycholic acid | 7172 ng/ml x h | Standard Error 852 |
| Metformin | Area-Under-the-Curve (AUC) of Endogenous Bile Acids After Polysorbate 80 | Taurochenodeoxycholic acid | 1467 ng/ml x h | Standard Error 204 |
| Metformin | Area-Under-the-Curve (AUC) of Endogenous Bile Acids After Polysorbate 80 | Lithocholic acid | 74.02 ng/ml x h | Standard Error 13.14 |
| Metformin | Area-Under-the-Curve (AUC) of Endogenous Bile Acids After Polysorbate 80 | Glycolithocholic acid | 165.3 ng/ml x h | Standard Error 32.3 |
| Metformin | Area-Under-the-Curve (AUC) of Endogenous Bile Acids After Polysorbate 80 | Taurolithocholic acid | 21.66 ng/ml x h | Standard Error 3.04 |
| Metformin | Area-Under-the-Curve (AUC) of Endogenous Bile Acids After Polysorbate 80 | Tauroursodeoxycholic acid | 19.79 ng/ml x h | Standard Error 3.81 |
| Metformin | Area-Under-the-Curve (AUC) of Endogenous Bile Acids After Polysorbate 80 | Ursodeoxycholic acid | 116.5 ng/ml x h | Standard Error 24.3 |
| Metformin | Area-Under-the-Curve (AUC) of Endogenous Bile Acids After Polysorbate 80 | Glycoursodeoxycholic acid | 415.5 ng/ml x h | Standard Error 57.4 |
| Placebo | Area-Under-the-Curve (AUC) of Endogenous Bile Acids After Polysorbate 80 | Glycochenodeoxycholic acid | 7386 ng/ml x h | Standard Error 847 |
| Placebo | Area-Under-the-Curve (AUC) of Endogenous Bile Acids After Polysorbate 80 | Cholic acid | 259.7 ng/ml x h | Standard Error 64.6 |
| Placebo | Area-Under-the-Curve (AUC) of Endogenous Bile Acids After Polysorbate 80 | Taurolithocholic acid | 21.02 ng/ml x h | Standard Error 4.55 |
| Placebo | Area-Under-the-Curve (AUC) of Endogenous Bile Acids After Polysorbate 80 | Glycocholic acid | 1053 ng/ml x h | Standard Error 187 |
| Placebo | Area-Under-the-Curve (AUC) of Endogenous Bile Acids After Polysorbate 80 | Taurochenodeoxycholic acid | 1393 ng/ml x h | Standard Error 195 |
| Placebo | Area-Under-the-Curve (AUC) of Endogenous Bile Acids After Polysorbate 80 | Taurocholic acid | 248.1 ng/ml x h | Standard Error 39.5 |
| Placebo | Area-Under-the-Curve (AUC) of Endogenous Bile Acids After Polysorbate 80 | Glycoursodeoxycholic acid | 542.1 ng/ml x h | Standard Error 181.9 |
| Placebo | Area-Under-the-Curve (AUC) of Endogenous Bile Acids After Polysorbate 80 | Deoxycholic acid | 1222 ng/ml x h | Standard Error 158 |
| Placebo | Area-Under-the-Curve (AUC) of Endogenous Bile Acids After Polysorbate 80 | Lithocholic acid | 67.64 ng/ml x h | Standard Error 14.64 |
| Placebo | Area-Under-the-Curve (AUC) of Endogenous Bile Acids After Polysorbate 80 | Glycodeoxycholic acid | 1507 ng/ml x h | Standard Error 200 |
| Placebo | Area-Under-the-Curve (AUC) of Endogenous Bile Acids After Polysorbate 80 | Ursodeoxycholic acid | 243.7 ng/ml x h | Standard Error 159.7 |
| Placebo | Area-Under-the-Curve (AUC) of Endogenous Bile Acids After Polysorbate 80 | Taurodeoxycholic acid | 329.3 ng/ml x h | Standard Error 53.1 |
| Placebo | Area-Under-the-Curve (AUC) of Endogenous Bile Acids After Polysorbate 80 | Glycolithocholic acid | 192.1 ng/ml x h | Standard Error 57.8 |
| Placebo | Area-Under-the-Curve (AUC) of Endogenous Bile Acids After Polysorbate 80 | Chenodeoxycholic acid | 5552 ng/ml x h | Standard Error 471 |
| Placebo | Area-Under-the-Curve (AUC) of Endogenous Bile Acids After Polysorbate 80 | Tauroursodeoxycholic acid | 17.07 ng/ml x h | Standard Error 3.33 |
p-value: <0.05t-test, 1 sided
Secondary
Peak Plasma Concentration (Cmax) of Endogenous Bile Acids After Metformin
For each of 15 endogenous bile acid, endogenous bile acid Cmax after metformin, compared to endogenous bile acid Cmax after placebo. Cmax units are concentration (i.e. ng/ml).
Time frame: 0-10 hours
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Metformin | Peak Plasma Concentration (Cmax) of Endogenous Bile Acids After Metformin | Glycodeoxycholic acid | 338.1 ng/ml | Standard Error 61.1 |
| Metformin | Peak Plasma Concentration (Cmax) of Endogenous Bile Acids After Metformin | Taurochenodeoxycholic acid | 192.9 ng/ml | Standard Error 32.9 |
| Metformin | Peak Plasma Concentration (Cmax) of Endogenous Bile Acids After Metformin | Glycocholic acid | 149.8 ng/ml | Standard Error 37.5 |
| Metformin | Peak Plasma Concentration (Cmax) of Endogenous Bile Acids After Metformin | Lithocholic acid | 10.88 ng/ml | Standard Error 1.62 |
| Metformin | Peak Plasma Concentration (Cmax) of Endogenous Bile Acids After Metformin | Taurodeoxycholic acid | 49.66 ng/ml | Standard Error 8.07 |
| Metformin | Peak Plasma Concentration (Cmax) of Endogenous Bile Acids After Metformin | Glycolithocholic acid | 36.20 ng/ml | Standard Error 6.84 |
| Metformin | Peak Plasma Concentration (Cmax) of Endogenous Bile Acids After Metformin | Deoxycholic acid | 234.0 ng/ml | Standard Error 44.9 |
| Metformin | Peak Plasma Concentration (Cmax) of Endogenous Bile Acids After Metformin | Taurolithocholic acid | 4.020 ng/ml | Standard Error 0.61 |
| Metformin | Peak Plasma Concentration (Cmax) of Endogenous Bile Acids After Metformin | Chenodeoxycholic acid | 2782 ng/ml | Standard Error 451 |
| Metformin | Peak Plasma Concentration (Cmax) of Endogenous Bile Acids After Metformin | Ursodeoxycholic acid | 65.54 ng/ml | Standard Error 39.4 |
| Metformin | Peak Plasma Concentration (Cmax) of Endogenous Bile Acids After Metformin | Taurocholic acid | 28.58 ng/ml | Standard Error 6.2 |
| Metformin | Peak Plasma Concentration (Cmax) of Endogenous Bile Acids After Metformin | Glycoursodeoxycholic acid | 121.5 ng/ml | Standard Error 42.6 |
| Metformin | Peak Plasma Concentration (Cmax) of Endogenous Bile Acids After Metformin | Glycochenodeoxycholic acid | 1338 ng/ml | Standard Error 267 |
| Metformin | Peak Plasma Concentration (Cmax) of Endogenous Bile Acids After Metformin | Tauroursodeoxycholic acid | 3.350 ng/ml | Standard Error 0.42 |
| Metformin | Peak Plasma Concentration (Cmax) of Endogenous Bile Acids After Metformin | Cholic acid | 109.6 ng/ml | Standard Error 40.5 |
| Placebo | Peak Plasma Concentration (Cmax) of Endogenous Bile Acids After Metformin | Tauroursodeoxycholic acid | 5.010 ng/ml | Standard Error 0.93 |
| Placebo | Peak Plasma Concentration (Cmax) of Endogenous Bile Acids After Metformin | Cholic acid | 123.8 ng/ml | Standard Error 51 |
| Placebo | Peak Plasma Concentration (Cmax) of Endogenous Bile Acids After Metformin | Glycocholic acid | 263.9 ng/ml | Standard Error 44.8 |
| Placebo | Peak Plasma Concentration (Cmax) of Endogenous Bile Acids After Metformin | Taurocholic acid | 67.64 ng/ml | Standard Error 12.96 |
| Placebo | Peak Plasma Concentration (Cmax) of Endogenous Bile Acids After Metformin | Deoxycholic acid | 199.7 ng/ml | Standard Error 28.6 |
| Placebo | Peak Plasma Concentration (Cmax) of Endogenous Bile Acids After Metformin | Glycodeoxycholic acid | 375.7 ng/ml | Standard Error 50.9 |
| Placebo | Peak Plasma Concentration (Cmax) of Endogenous Bile Acids After Metformin | Taurodeoxycholic acid | 86.14 ng/ml | Standard Error 16.5 |
| Placebo | Peak Plasma Concentration (Cmax) of Endogenous Bile Acids After Metformin | Chenodeoxycholic acid | 2982 ng/ml | Standard Error 359 |
| Placebo | Peak Plasma Concentration (Cmax) of Endogenous Bile Acids After Metformin | Glycochenodeoxycholic acid | 1667 ng/ml | Standard Error 234 |
| Placebo | Peak Plasma Concentration (Cmax) of Endogenous Bile Acids After Metformin | Taurochenodeoxycholic acid | 349.8 ng/ml | Standard Error 69.7 |
| Placebo | Peak Plasma Concentration (Cmax) of Endogenous Bile Acids After Metformin | Lithocholic acid | 9.400 ng/ml | Standard Error 2.04 |
| Placebo | Peak Plasma Concentration (Cmax) of Endogenous Bile Acids After Metformin | Glycolithocholic acid | 43.31 ng/ml | Standard Error 12.76 |
| Placebo | Peak Plasma Concentration (Cmax) of Endogenous Bile Acids After Metformin | Taurolithocholic acid | 6.150 ng/ml | Standard Error 1.8 |
| Placebo | Peak Plasma Concentration (Cmax) of Endogenous Bile Acids After Metformin | Ursodeoxycholic acid | 41.60 ng/ml | Standard Error 24.98 |
| Placebo | Peak Plasma Concentration (Cmax) of Endogenous Bile Acids After Metformin | Glycoursodeoxycholic acid | 118.0 ng/ml | Standard Error 38.3 |
p-value: <0.05t-test, 1 sided
Secondary
Peak Plasma Concentration (Cmax) of Endogenous Bile Acids After Polysorbate 80
For each of 15 endogenous bile acid, endogenous bile acid Cmax after polysorbate 80, compared to endogenous bile acid Cmax after placebo. Cmax units are concentration (i.e. ng/ml).
Time frame: 0-10 hours
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Metformin | Peak Plasma Concentration (Cmax) of Endogenous Bile Acids After Polysorbate 80 | Glycodeoxycholic acid | 385.7 ng/ml | Standard Error 43.5 |
| Metformin | Peak Plasma Concentration (Cmax) of Endogenous Bile Acids After Polysorbate 80 | Taurochenodeoxycholic acid | 332.6 ng/ml | Standard Error 47.4 |
| Metformin | Peak Plasma Concentration (Cmax) of Endogenous Bile Acids After Polysorbate 80 | Glycocholic acid | 291.3 ng/ml | Standard Error 35.5 |
| Metformin | Peak Plasma Concentration (Cmax) of Endogenous Bile Acids After Polysorbate 80 | Lithocholic acid | 12.35 ng/ml | Standard Error 2.59 |
| Metformin | Peak Plasma Concentration (Cmax) of Endogenous Bile Acids After Polysorbate 80 | Taurodeoxycholic acid | 92.58 ng/ml | Standard Error 13.42 |
| Metformin | Peak Plasma Concentration (Cmax) of Endogenous Bile Acids After Polysorbate 80 | Glycolithocholic acid | 36.68 ng/ml | Standard Error 7.81 |
| Metformin | Peak Plasma Concentration (Cmax) of Endogenous Bile Acids After Polysorbate 80 | Deoxycholic acid | 270.9 ng/ml | Standard Error 49.4 |
| Metformin | Peak Plasma Concentration (Cmax) of Endogenous Bile Acids After Polysorbate 80 | Taurolithocholic acid | 5.510 ng/ml | Standard Error 0.76 |
| Metformin | Peak Plasma Concentration (Cmax) of Endogenous Bile Acids After Polysorbate 80 | Chenodeoxycholic acid | 3049 ng/ml | Standard Error 280 |
| Metformin | Peak Plasma Concentration (Cmax) of Endogenous Bile Acids After Polysorbate 80 | Ursodeoxycholic acid | 27.89 ng/ml | Standard Error 5.3 |
| Metformin | Peak Plasma Concentration (Cmax) of Endogenous Bile Acids After Polysorbate 80 | Taurocholic acid | 77.80 ng/ml | Standard Error 10.81 |
| Metformin | Peak Plasma Concentration (Cmax) of Endogenous Bile Acids After Polysorbate 80 | Glycoursodeoxycholic acid | 86.27 ng/ml | Standard Error 12.4 |
| Metformin | Peak Plasma Concentration (Cmax) of Endogenous Bile Acids After Polysorbate 80 | Glycochenodeoxycholic acid | 1396 ng/ml | Standard Error 175 |
| Metformin | Peak Plasma Concentration (Cmax) of Endogenous Bile Acids After Polysorbate 80 | Tauroursodeoxycholic acid | 5.360 ng/ml | Standard Error 0.77 |
| Metformin | Peak Plasma Concentration (Cmax) of Endogenous Bile Acids After Polysorbate 80 | Cholic acid | 91.16 ng/ml | Standard Error 21.41 |
| Placebo | Peak Plasma Concentration (Cmax) of Endogenous Bile Acids After Polysorbate 80 | Tauroursodeoxycholic acid | 5.010 ng/ml | Standard Error 0.93 |
| Placebo | Peak Plasma Concentration (Cmax) of Endogenous Bile Acids After Polysorbate 80 | Cholic acid | 123.8 ng/ml | Standard Error 51 |
| Placebo | Peak Plasma Concentration (Cmax) of Endogenous Bile Acids After Polysorbate 80 | Glycocholic acid | 263.9 ng/ml | Standard Error 44.8 |
| Placebo | Peak Plasma Concentration (Cmax) of Endogenous Bile Acids After Polysorbate 80 | Taurocholic acid | 67.64 ng/ml | Standard Error 12.96 |
| Placebo | Peak Plasma Concentration (Cmax) of Endogenous Bile Acids After Polysorbate 80 | Deoxycholic acid | 199.7 ng/ml | Standard Error 28.6 |
| Placebo | Peak Plasma Concentration (Cmax) of Endogenous Bile Acids After Polysorbate 80 | Glycodeoxycholic acid | 375.7 ng/ml | Standard Error 50.9 |
| Placebo | Peak Plasma Concentration (Cmax) of Endogenous Bile Acids After Polysorbate 80 | Taurodeoxycholic acid | 86.14 ng/ml | Standard Error 16.5 |
| Placebo | Peak Plasma Concentration (Cmax) of Endogenous Bile Acids After Polysorbate 80 | Chenodeoxycholic acid | 2982 ng/ml | Standard Error 359 |
| Placebo | Peak Plasma Concentration (Cmax) of Endogenous Bile Acids After Polysorbate 80 | Glycochenodeoxycholic acid | 1667 ng/ml | Standard Error 234 |
| Placebo | Peak Plasma Concentration (Cmax) of Endogenous Bile Acids After Polysorbate 80 | Taurochenodeoxycholic acid | 349.8 ng/ml | Standard Error 69.7 |
| Placebo | Peak Plasma Concentration (Cmax) of Endogenous Bile Acids After Polysorbate 80 | Lithocholic acid | 9.400 ng/ml | Standard Error 2.04 |
| Placebo | Peak Plasma Concentration (Cmax) of Endogenous Bile Acids After Polysorbate 80 | Glycolithocholic acid | 43.31 ng/ml | Standard Error 12.76 |
| Placebo | Peak Plasma Concentration (Cmax) of Endogenous Bile Acids After Polysorbate 80 | Taurolithocholic acid | 6.150 ng/ml | Standard Error 1.8 |
| Placebo | Peak Plasma Concentration (Cmax) of Endogenous Bile Acids After Polysorbate 80 | Ursodeoxycholic acid | 41.60 ng/ml | Standard Error 24.98 |
| Placebo | Peak Plasma Concentration (Cmax) of Endogenous Bile Acids After Polysorbate 80 | Glycoursodeoxycholic acid | 118.0 ng/ml | Standard Error 38.3 |
p-value: <0.05t-test, 1 sided