Milk thistle supplement raises resmetirom exposure in a rat MASH model
- Milk thistle (silybin) given with the liver-directed THR-β agonist resmetirom to MCD-diet MASH rats increased resmetirom plasma exposure and lowered its apparent oral clearance.
- In rat liver microsomes, the extract markedly slowed resmetirom depletion, pointing to inhibited hepatic metabolism.
- The combination also improved liver enzymes, lipids and histology more than either agent alone, though the exposure increase flags a possible interaction.
💡 Points
A rat MCD-diet model is a rough proxy for human MASH, and a rat microsomal slowdown says little about the CYP and transporter picture in people. Still, higher exposure in a liver-directed drug is exactly what I'd chase: is the extra efficacy just more drug on board, and does the safety margin shrink with it? Needs human PK before anyone reads it as benefit.