Proton Pump Inhibitor Co-medication Reduces Active Drug Exposure in Heart Transplant Recipients Receiving Mycophenolate Mofetil

Abstract Background Proton pump inhibitors (PPIs) are often prescribed for gastrointestinal discomfort after heart transplantation. This study investigated the impact of PPI use on mycophenolic acid (MPA) pharmacokinetics in heart transplant recipients receiving mycophenolate mofetil (MMF) in combin...

Full description

Saved in:
Bibliographic Details
Published in:Transplantation proceedings 2010-12, Vol.42 (10), p.4243-4246
Main Authors: Doesch, A.O, Mueller, S, Konstandin, M, Celik, S, Erbel, C, Kristen, A, Frankenstein, L, Koch, A, Ehlermann, P, Zugck, C, Katus, H.A
Format: Article
Language:English
Subjects:
Aged
Antibiotics. Antiinfectious agents. Antiparasitic agents
Antiviral agents
Area Under Curve
Biological and medical sciences
Drug Therapy, Combination
Female
Fundamental and applied biological sciences. Psychology
Fundamental immunology
Heart Transplantation
Humans
Immunosuppressive Agents - administration & dosage
Immunosuppressive Agents - pharmacokinetics
Male
Medical sciences
Middle Aged
Mycophenolic Acid - administration & dosage
Mycophenolic Acid - analogs & derivatives
Mycophenolic Acid - pharmacokinetics
Pharmacology. Drug treatments
Proton Pump Inhibitors - administration & dosage
Surgery
Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases
Tissue, organ and graft immunology
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Abstract Background Proton pump inhibitors (PPIs) are often prescribed for gastrointestinal discomfort after heart transplantation. This study investigated the impact of PPI use on mycophenolic acid (MPA) pharmacokinetics in heart transplant recipients receiving mycophenolate mofetil (MMF) in combination with a calcineurin inhibitor (tacrolimus [TAC]/cyclosporine [CsA]) or mammalian target of rapamycin inhibitor (sirolimus/everolimus). Methods Abbreviated MPA areas under the curve (AUCs; 0, 30, and 120 minutes after morning intake) were obtained in 19 patients on a PPI (initial examination) and 1 month after PPI discontinuation (follow-up). Mean patient age was 58.2 ± 8.8 years, and mean time after transplantation was 2.3 ± 4.0 years (range, 0.2–13.0 years). Results At initial examination mean daily MMF dose was 2.2 ± 0.8 g. MMF dose was kept unchanged for the duration of study ( P = ns). Mean predose (C0) MPA serum concentrations were insignificantly lower with PPI comedication (2.5 ± 2.2 mg/L vs 2.8 ± 1.7 mg/L; P = .15). Dose-adjusted abbreviated MPA AUCs (adjusted to morning dose) were significantly lower during PPI therapy (45.2 ± 20.3 vs 65.2 ± 38.8 mg · h/L · g [MMF]; P = .02). Conclusions Patients with PPI comedication during MMF therapy show significantly lower exposure to mycophenolic acid determined by dose-adjusted abbreviated MPA AUCs. Although the clinical relevance of this pharmacokinetic interaction was not determined in this study, MPA drug monitoring by limited sampling strategies might be helpful during changes in antacid comedication in patients on MMF.
ISSN:0041-1345
1873-2623
DOI:10.1016/j.transproceed.2010.09.047