NCT04640571

Impact of Metformin and Polysorbate 80 on Drug Absorption and Disposition

• Status: Completed
• Phase: Phase 4
• Study type: Interventional
• Enrollment: 18 (actual)
• Sponsor: University of Maryland, Baltimore · Academic / Other
• Sex: All
• Age: 18 Years – 65 Years
• Healthy volunteers: Accepted

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.

Conditions

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

Interventions

Type	Name	Description
DRUG	pravastatin and chenodeoxycholic acid, after metformin and placebo	single oral dose of pravastatin 80 mg and chenodeoxycholic acid 250 mg
DRUG	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

Timeline

• Start date: 2021-04-01
• Primary completion: 2021-11-01
• Completion: 2021-11-01
• First posted: 2020-11-23
• Last updated: 2024-07-16
• Results posted: 2024-07-16

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study