No relevant pharmacokinetic interaction between pantoprazole and mycophenolate in renal transplant patients: a randomized crossover study.
Rissling O, Glander P, et al.British Journal of Clinical Pharmacology 2015; 80(5): 1086-1096.
Aims
To evaluate the drug–drug interaction (DDA) of pantoprazole (PAN) on the bioavailability of Mycophenolic acid (MPA) after mycophenolate mofetil (MMF) or enteric-coated mycophenolate sodium (EC-MPS) intake in stable renal allograft recipients.
Interventions
Patients were randomized to a four sequence, four period, four-treatment crossover design, and received MMF, EC-MPS, EC-MPS+PAN and MMF+PAN, with each treatment period lasting 2 weeks.
Participants
20 adult (≥18 years) stable renal allograft recipients, who were ≥ 6months posttransplant and receiving ciclosporin with or without glucocorticoids.
Outcomes
The primary outcome was the bioavailability of MPA after MMF and EC-MPS application alone or in combination with PAN.
Follow-up
12 hours
CET Conclusions
Proton pump inhibitors such as pantoprazole have been known to interfere with the release of other drugs through an increase in stomach pH. There is some evidence that PPIs can alter the hydrolysis and conversion of the pro-drug Myophenolate Mofetil (MMF) to Mycophenolic Acid. This study was an open-label, RCT in a cross-over design that was well conducted and reported. The effects of pantoprazole on MMF and Enteric-Coated MPS pharmacodynamics and pharmacokinetics were assessed in stable renal transplant recipients. The study was powered for a 25% reduction in bio-availability. The results suggested that there may be an 11% difference between AUC for MMF and Pantoprazole compared to MMF alone but the study was not large enough to truly demonstrate this. There was no other impact on Mycophenolic Acid pharmacodynamics. The immune suppressive effect was unchanged.
Data analysis
Per protocol analysis
Trial registration
Eudra-CT number - 2010-021275-92; ClinicalTrials.gov - NCT01801280