title: 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 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.
authors.affiliation: Department of Cardiology, University of Heidelberg, Heidelberg, Germany. Andreas.Doesch@med.uni-heidelberg.de
authors.forename: A O
authors.initials: AO
authors.lastname: Doesch
authors.forename: S
authors.initials: S
authors.lastname: Mueller
authors.forename: M
authors.initials: M
authors.lastname: Konstandin
authors.forename: S
authors.initials: S
authors.lastname: Celik
authors.forename: C
authors.initials: C
authors.lastname: Erbel
authors.forename: A
authors.initials: A
authors.lastname: Kristen
authors.forename: L
authors.initials: L
authors.lastname: Frankenstein
authors.forename: A
authors.initials: A
authors.lastname: Koch
authors.forename: P
authors.initials: P
authors.lastname: Ehlermann
authors.forename: C
authors.initials: C
authors.lastname: Zugck
authors.forename: H A
authors.initials: HA
authors.lastname: Katus
mesh_terms: D000368:Aged; D019540:Area Under Curve; D004359:Drug Therapy, Combination; D005260:Female; D016027:Heart Transplantation; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D054328:Proton Pump Inhibitors / Q000008:administration & dosage*
chemical_list: D007166:Immunosuppressive Agents; D054328:Proton Pump Inhibitors; D009173:Mycophenolic Acid