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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
NONE
Enrollment
18
single oral dose of pravastatin 80 mg and chenodeoxycholic acid 250 mg
single oral dose of valacyclovir 500 mg, chenodeoxycholic acid 250 mg, and enalaprilat 20 mg
University of Maryland
Baltimore, Maryland, United States
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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