Effect of the proton-pump Inhibitor pantoprazole on MycoPhenolic ACid exposure in kidney and liver transplant recipienTs (IMPACT study): a randomized trial

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dc.contributor.authorSunderland, A.
dc.contributor.authorRuss, G.
dc.contributor.authorSallustio, B.
dc.contributor.authorCervelli, M.
dc.contributor.authorJoyce, D.
dc.contributor.authorOoi, E.
dc.contributor.authorJeffrey, G.
dc.contributor.authorBoudville, N.
dc.contributor.authorChakera, A.
dc.contributor.authorDogra, G.
dc.contributor.authorChan, D.
dc.contributor.authorWong, G.
dc.contributor.authorLim, W.H.
dc.date.issued2020
dc.description.abstractBACKGROUND:Mycophenolic acid (MPA) is widely utilized as an immunosuppressant in kidney and liver transplantation, with reports suggesting an independent relationship between MPA concentrations and adverse allograft outcome. Proton-pump inhibitors (PPIs) may have variable effects on the absorption of different MPA formulations leading to differences in MPA exposure. METHODS:A multicentre, randomized, prospective, double-blind placebo-controlled cross-over study was conducted to determine the effect of the PPI pantoprazole on the MPA and its metabolite MPA-glucuronide (MPA-G) area under the curve (AUC) >12 h (MPA-AUC12 h) in recipients maintained on mycophenolate mofetil (MMF) or enteric-coated mycophenolate sodium (EC-MPS). We planned a priori to examine separately recipients maintained on MMF and EC-MPS for each pharmacokinetic parameter. The trial (and protocol) was registered with the Australian New Zealand Clinical Trials Registry on 24 March 2011, with the registration number of ACTRN12611000316909 ('IMPACT' study). RESULTS:Of the 45 recipients screened, 40 (19 MMF and 21 EC-MPS) were randomized. The mean (standard deviation) recipient age was 58 (11) years with a median (interquartile range) time post-transplant of 43 (20-132) months. For recipients on MMF, there was a significant reduction in the MPA-AUC12 h [geometric mean (95% confidence interval) placebo: 53.9 (44.0-65.9) mg*h/L versus pantoprazole: 43.8 (35.6-53.4) mg*h/L; P = 0.004] when pantoprazole was co-administered compared with placebo. In contrast, co-administration with pantoprazole significantly increased MPA-AUC12 h [placebo: 36.1 (26.5-49.2) mg*h/L versus pantoprazole: 45.9 (35.5-59.3) mg*h/L; P = 0.023] in those receiving EC-MPS. Pantoprazole had no effect on the pharmacokinetic profiles of MPA-G for either group. CONCLUSIONS:The co-administration of pantoprazole substantially reduced the bioavailability of MPA in patients maintained on MMF and had the opposite effect in patients maintained on EC-MPS, and therefore, clinicians should be cognizant of this drug interaction when prescribing the different MPA formulations.
dc.description.statementofresponsibilityAndrew Sunderland, Graeme Russ, Benedetta Sallustio, Matthew Cervelli, David Joyce, Esther Ooi ... et al.
dc.identifier.citationNephrology Dialysis Transplantation, 2020; 35(6):1060-1070
dc.identifier.doi10.1093/ndt/gfaa111
dc.identifier.issn0931-0509
dc.identifier.issn1460-2385
dc.identifier.orcidSallustio, B. [0000-0002-0186-3073]
dc.identifier.urihttp://hdl.handle.net/2440/126927
dc.language.isoen
dc.publisherOxford University Press
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/102538
dc.rights© The Author(s) 2020. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.
dc.source.urihttps://doi.org/10.1093/ndt/gfaa111
dc.subjectdrug interaction
dc.subjectenteric-coated mycophenolate sodium
dc.subjectkidney transplant
dc.subjectmycophenolate
dc.subjectmycophenolic acid
dc.subjectpharmacokinetic
dc.subjectproton-pump inhibitor
dc.titleEffect of the proton-pump Inhibitor pantoprazole on MycoPhenolic ACid exposure in kidney and liver transplant recipienTs (IMPACT study): a randomized trial
dc.typeJournal article
pubs.publication-statusPublished

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