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Sites of gastrointestinal lesion induced by mycophenolate mofetil: a comparison with enteric-coated mycophenolate

Yichen Jia1, Rulin Wang2, Long Li1

  • 1Department of Urology, Shanghai Key laboratory of Organ Transplantation, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032, People's Republic of China.

BMC Pharmacology & Toxicology
|July 6, 2018
PubMed
Abstract

Insights

Mycophenolate mofetil (MMF) causes significant gastrointestinal injury, particularly in the jejunum and ileum. Enteric-coated mycophenolate sodium (EC-MPS) results in less GI damage due to its delayed absorption.

Area of Science:

  • Pharmacology
  • Gastroenterology
  • Transplantation Medicine

Background:

  • Renal transplant immunosuppressants mycophenolate mofetil (MMF) and enteric-coated mycophenolate sodium (EC-MPS) are known to cause gastrointestinal (GI) disorders.
  • The precise location within the GI tract affected by MMF and EC-MPS remains incompletely understood.

Purpose of the Study:

  • To investigate the specific effects of MMF and EC-MPS on different segments of the rat GI tract.
  • To compare the GI injury profiles of MMF and EC-MPS.

Main Methods:

  • A rat model was used, with five groups: control, MMF, mofetil, EC-MPS, and a combination group.
  • Drug administration was via intra-gastric gavage daily for 7 days.
  • Diarrhea grade, body weight, and histological changes in GI tissues (stomach, duodenum, jejunum, ileum, colon, rectum) were assessed.

Main Results:

  • MMF treatment led to significantly higher diarrhea grade and weight loss compared to other groups.
  • Histological analysis revealed significantly higher pathological scores in the jejunum and ileum of the MMF group versus the EC-MPS groups.
  • MMF showed higher concentrations of mycophenolic acid glucuronide (MPAG) in the jejunum and ileum compared to EC-MPS, suggesting MMF targets these segments.

Conclusions:

  • MMF appears to specifically target the jejunum and ileum, inducing GI injury.
  • EC-MPS causes less GI injury than MMF, likely attributable to its delayed absorption kinetics.
Keywords:
Enteric-coated mycophenolate sodiumGI side effectsMycophenolate mofetilPharmacokinetics

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