Impact of Metformin and Polysorbate 80 on Drug Absorption and Disposition
Status:
Recruiting
Trial end date:
2022-01-01
Target enrollment:
Participant gender:
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.