Impact of Metformin and Polysorbate 80 on Drug Absorption and Disposition

Conditions

• Bile Salt Export Pump (BSEP) Transporter
• Polysorbate 80

Eligibility Criteria

Sex

ALL

Age

18 Years - 65 Years

Healthy Volunteers

Accepted

Interventions

• pravastatin and chenodeoxycholic acid, after metformin and placebo — DRUG
  single oral dose of pravastatin 80 mg and chenodeoxycholic acid 250 mg
• valacyclovir, chenodeoxycholic acid, and enalaprilat, after polysorbate 80 and placebo — DRUG
  single oral dose of valacyclovir 500 mg, chenodeoxycholic acid 250 mg, and enalaprilat 20 mg

Study Details

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.

Key Dates

Start date

Apr 1, 2021

Status verified

Jul 2024

Primary completion

Nov 1, 2021

Completion

Nov 1, 2021

Study Design

Enrollment

18 participants (actual)

Allocation

RANDOMIZED

Intervention model

CROSSOVER

Primary purpose

BASIC_SCIENCE

Arms

• Experimental: 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
• Experimental: 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
• Experimental: 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
• Experimental: 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
• Experimental: 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
• Experimental: 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

Primary Outcome Measure

Area-Under-the-Curve (AUC) of Pravastatin After Metformin [ Time Frame: 0-10 hours ]

Locations (1)

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