Gut Microbiota-Mediated Pharmacokinetic Drug-Drug Interactions between Mycophenolic Acid and Trimethoprim-Sulfamethoxazole in Humans

The study aimed to investigate the impact of TMP-SMX on the pharmacokinetics of MPA and its relationship with gut microbiota in humans. 16 healthy volunteers took a single dose of 1,000mg of mycophenolate mofetil (MMF), a prodrug of MPA, both alone and with concurrent use of TMP-SMX for 5 days. The levels of MPA and its glucuronide (MPAG) were measured and the gut microbiome was analyzed before and after TMP-SMX treatment. The findings suggest that the drug interaction between TMP-SMX and MPA might be caused by the impact of TMP-SMX's broad-spectrum antibiotic properties on gut bacteria-mediated MPA metabolism.