Impact of Metformin and Polysorbate 80 on Drug Absorption and Disposition
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.
Timeline
- Start
- 2021-04-01
- Primary completion
- 2021-11-01
- Completion
- 2021-11-01
Drugs
| Evaluation | Drug | Modality | Dose | Route |
|---|---|---|---|---|
| Subject | Chenodeoxycholic Acid | Small molecule | 250 mg | Oral |
| Subject | ENALAPRILAT ANHYDROUS | Small molecule | 20 mg | Oral |
| Subject | Metformin | Small molecule | 500 mg | — |
| Subject | Pravastatin | Small molecule | 80 mg | Oral |
| Subject | Valacyclovir | Unknown | 500 mg | Oral |
| Subject | polysorbate 80 | Small molecule | 400 mg | — |
Indications
No indication recorded.