The proton pump inhibitor pantoprazole and its interaction with enteric-coated mycophenolate sodium in transplant recipients

Kofler, Sieglinde; Wolf, Christine; Shvets, N. V.; Sisic, Zeljka; Müller, Thomas; Behr, Jürgen; Sohn, Hae-Young; Vogeser, Michael; Shipkova, Maria; Meiser, Bruno; Steinbeck, Gerhard; Reichart, Bruno; Kaczmarek, Ingo

doi:10.1016/j.healun.2010.12.003

Cited by 29 publications

(21 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…As a result, strict bioequivalence criteria are not fulfilled when PAN is added to one of the MPA formulations. Similarly to previous studies in healthy volunteers or heart transplant patients , differences in dCmax and dAUC values did not reach statistical significance with EC‐MPS. Other studies found a significant decrease in MPA exposure and/or Cmax values after concomitant therapy with PAN and MMF.…”

Section: Discussionsupporting

confidence: 62%

See 1 more Smart Citation

No relevant pharmacokinetic interaction between pantoprazole and mycophenolate in renal transplant patients: a randomized crossover study

Rissling

Glander

Hambach

et al. 2015

Brit J Clinical Pharma

View full text Add to dashboard Cite

AIMSMycophenolic acid (MPA) suppresses lymphocyte proliferation through inosine monophosphate dehydrogenase (IMPDH) inhibition. Two formulations have been approved: mycophenolate mofetil (MMF) and enteric-coated mycophenolate sodium (EC-MPS). Pantoprazole (PAN) inhibits gastric acid secretion, which may alter MPA exposure. Data from healthy volunteers suggest a significant drug-drug interaction (DDA) between pantoprazole and MPA. In transplant patients, a decreased MPA area under the concentration-time curve (AUC) may lead to higher IMPDH activity, which may lead to higher acute rejection risk. Therefore this DDA was evaluated in renal transplant patients under maintenance immunosuppressive therapy. METHODSIn this single-centre, open, randomized, four-sequence, four-treatment crossover study, the influence of PAN 40 mg on MPA pharmacokinetics such as (dose-adjusted) AUC 0-12 h (dAUC) was analysed in 20 renal transplant patients (>6 months post-transplantation) receiving MMF (1-2 g day -1) and EC-MPS in combination with ciclosporin. The major metabolite MPA glucuronide (MPAG) and the IMPDH activity were also examined. RESULTS MMF CONCLUSIONPantoprazole influences EC-MPS and MMF pharmacokinetics but as it had no impact on MPA pharmacodynamics, the immunosuppressive effect of the drug was not impaired. WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT• Pantoprazole is a frequently prescribed proton pump inhibitor (PPI) in renal transplant patients as gastrointestinal side effects, such as heartburn, are common under immunosuppressive therapy with mycophenolate.• PPIs influence the bioavailability of drugs by raising gastric pH, which may lead to different dissolution rates or changes in the solubility of drugs. WHAT THIS STUDY ADDS• This crossover study analysed the effect of pantoprazole on MMF and EC-MPS pharmacokinetics in renal transplant patients under maintenance immunosuppressive therapy.• For pantoprazole intake, bioequivalence was not established for either MMF or EC-MPS.• Further analysis showed no impact of pantoprazole on MPAG pharmacokinetics or MPA pharmacodynamics.

show abstract

Section: Discussionsupporting

confidence: 62%

“…By contrast, for the EC-MPS tablet, fast dissolution was found to be achieved at pH >5.5 [7]. MPA absorption seems not to be affected by PPIs in healthy volunteers or in heart transplant patients [7][8][9].…”

Section: Introductionmentioning

confidence: 86%

No relevant pharmacokinetic interaction between pantoprazole and mycophenolate in renal transplant patients: a randomized crossover study

Rissling

Glander

Hambach

et al. 2015

Brit J Clinical Pharma

View full text Add to dashboard Cite

show abstract

“…Although data to support conversion from MMF to EC-MPS for gastrointestinal adverse events are limited to open-label, crossover studies, pharmacokinetic studies have shown that MPA exposure in patients given EC-MPS is not adversely effected by PPI (19,25,27). Because a generic is not available, EC-MPS remains a more expensive but potential alternative to MMF in patients requiring a PPI who are at high risk for rejection.…”

Section: Discussionmentioning

confidence: 99%

Concomitant Proton Pump Inhibitors With Mycophenolate Mofetil and the Risk of Rejection in Kidney Transplant Recipients

et al. 2014

View full text Add to dashboard Cite

show abstract

“…At least for heart transplant recipients no influence of pantoprazole on EC-MPS pharmacokinetics could be disclosed (43).…”

Section: Effect Of Concomitant Therapy On Mpa Pharmacokineticsmentioning

confidence: 99%

Pharmacokinetics and Pharmacodynamics of Mycophenolate in Patients After Renal Transplantation

Rath¹,

Küpper²

2012

Renal Transplantation - Updates and Advances

View full text Add to dashboard Cite

The proton pump inhibitor pantoprazole and its interaction with enteric-coated mycophenolate sodium in transplant recipients

Cited by 29 publications

References 29 publications

No relevant pharmacokinetic interaction between pantoprazole and mycophenolate in renal transplant patients: a randomized crossover study

No relevant pharmacokinetic interaction between pantoprazole and mycophenolate in renal transplant patients: a randomized crossover study

Concomitant Proton Pump Inhibitors With Mycophenolate Mofetil and the Risk of Rejection in Kidney Transplant Recipients

Pharmacokinetics and Pharmacodynamics of Mycophenolate in Patients After Renal Transplantation

Contact Info

Product

Resources

About