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Gut Microbiota-Mediated Pharmacokinetic Drug-Drug Interactions between Mycophenolic Acid and

Nahathai Dukaew1,2, Patcharawadee Thongkumkoon3, Nutnicha Sirikaew3

  • 1Department of Pharmacology, Faculty of Medicine, Chiang Mai University, 110 Intawaroros Road, Sriphoom, Muang, Chiang Mai 50200, Thailand.

Pharmaceutics
|June 28, 2023
PubMed

Insights

Trimethoprim-sulfamethoxazole (TMP-SMX) reduces mycophenolic acid (MPA) exposure by altering gut microbiota. This drug interaction, important for transplant patients, highlights the impact of antibiotics on MPA pharmacokinetics.

Area of Science:

  • Pharmacology
  • Microbiology
  • Drug Interactions

Background:

  • Mycophenolic acid (MPA) and trimethoprim-sulfamethoxazole (TMP-SMX) are frequently co-prescribed, particularly in solid organ transplant recipients.
  • The pharmacokinetic drug-drug interactions (DDIs) between MPA and TMP-SMX are not well understood.

Purpose of the Study:

  • To investigate the impact of TMP-SMX on MPA pharmacokinetics in healthy volunteers.
  • To explore the relationship between MPA pharmacokinetics and alterations in gut microbiota composition.

Main Methods:

  • 16 healthy volunteers received mycophenolate mofetil (MMF) alone and concurrently with TMP-SMX.
  • Pharmacokinetic parameters of MPA and its metabolite MPAG were quantified using high-performance liquid chromatography.
  • Gut microbiota composition was analyzed via 16S rRNA sequencing before and after TMP-SMX treatment.

Main Results:

  • Coadministration of TMP-SMX significantly decreased systemic MPA exposure.
  • TMP-SMX treatment altered the relative abundance of gut bacterial genera, notably *Bacteroides* and *Faecalibacterium*.
  • Specific bacterial genera, including *Bacteroides* and *Ruminococcus*, showed significant correlations with systemic MPA exposure.

Conclusions:

  • TMP-SMX reduces systemic MPA exposure through its effects on gut microbiota-mediated metabolism.
  • These findings elucidate a key pharmacokinetic DDI relevant to patient populations receiving both medications.
Keywords:
drug–drug interactiongut microbiotamycophenolate mofetilmycophenolic acidpharmacokineticstrimethoprim-sulfamethoxazole

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