Correlation between Area Under the Concentration-Time Curve of Mycophenolate Mofetil and its Gastrointestinal Tolerability in Renal Transplant Recipients

Background Mycophenolate mofetil (MMF) is a key drug in the triple immunosuppressant regimen for preventing renal allograft rejection in renal transplant recipients (RTRs). Common gastrointestinal (GI) adverse effects include abdominal discomfort (14-63%), vomiting (29-39%), and diarrhea (24-53%). Diarrhea often occurs without an underlying GI infection. While MMF’s efficacy correlates with drug exposure, the relationship between adverse effects and drug levels is unclear. This study was conducted to understand whether the GI adverse effects due to MMF has any bearing with the exposure of MPA or MPAG. Materials and Methods A prospective study was conducted after obtaining the Institutional Ethics Committee approval. Patients ≥18 years, post-renal transplantation (>4 weeks), on MMF, and reporting chronic diarrhea were included (n=30). A control group (n=10) comprised patients without diarrhea. Blood samples were collected 0, 1, 2, 4, and 6 hours post-MMF administration. AUC 0-12 levels of MPA and MPA glucuronide MPAG were measured using high-performance liquid chromatography (HPLC)-UV. Results The primary causes of ESRD were idiopathic (40%) and chronic glomerulonephritis (33%). All participants were on tacrolimus, MMF, and steroids. There was no significant difference in AUC 0-12 levels of MPA (P=0.24) or MPAG (P=0.84) between the diarrhea and control groups. Conclusion No significant association was found between MPA or MPAG exposure and chronic diarrhea in kidney transplant recipients. These findings suggest that MPA and MPAG levels are not predictive of chronic diarrhea, highlighting the need to explore other factors, such as alterations in the gut microbiome.