title: The role of proton pump inhibitors on early mycophenolic acid exposure in kidney transplantation: evidence from the CLEAR study.
abstract: BACKGROUND
  Proton pump inhibitors (PPIs) are often prescribed posttransplantation to prevent gastrointestinal complications. A series of recent studies have reported a relationship between PPI comedication and decreased mycophenolic acid (MPA) exposure. The objective of this subanalysis of the CLEAR data set was to determine the impact of PPI therapy on full MPA area under the curve exposures at Day 5 post kidney transplant.
  
  
  METHODS
  Patients were randomized to receive either intensified dosing of mycophenolate mofetil (1.5 g twice daily on Days 1-5, then 1.0 g twice daily, n = 68) or standard dosing (1.0 g twice daily, n = 67). All recipients received tacrolimus and prednisone.
  
  
  RESULTS
  In the modified intention-to-treat population, 57.9% of patients (73 of 126) received PPI therapy. The most frequently administered therapies were pantoprazole and omeprazole. There was no significant difference in mean MPA area under the curve at Day 5 for patients receiving PPI therapy as compared with those not receiving PPI therapy (51.3 versus 55.8 mg.h/L, P = 0.265). However, the MPA concentration-time curve analysis demonstrated a significant decrease in MPA concentrations at 2 hours and 12 hours postdose in patients receiving PPI therapy (P = 0.0009 and P = 0.034). No significant differences were identified in the 3-g arm specifically. In the multivariate model, only serum creatinine and albumin significantly predicted MPA area under the curve less than 30 mg.h/L at Day 5.
  
  
  CONCLUSIONS
  PPI therapy in combination with mycophenolate mofetil does not appear to have a significant impact on full MPA exposure. Because MPA pharmacokinetics were not significantly impacted when a 3-g, 5-day loading dose of mycophenolate mofetil was used in combination with PPI therapy, this strategy may be required for adequate MPA exposure whether or not a patient receives PPI comedication.
authors.affiliation: QEII Health Sciences Centre, Halifax, Nova Scotia, Canada. bryce.kiberd@dal.ca
authors.forename: Bryce A
authors.initials: BA
authors.lastname: Kiberd
authors.forename: Michelle
authors.initials: M
authors.lastname: Wrobel
authors.forename: Raymond
authors.initials: R
authors.lastname: Dandavino
authors.forename: Paul
authors.initials: P
authors.lastname: Keown
authors.forename: Sita
authors.initials: S
authors.lastname: Gourishankar
mesh_terms: D019540:Area Under Curve; D003404:Creatinine; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D005260:Female; D005767:Gastrointestinal Diseases / Q000150:complications / Q000517:prevention & control*; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D016030:Kidney Transplantation; D008297:Male; D009173:Mycophenolic Acid / Q000008:administration & dosage* / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D011241:Prednisone / Q000627:therapeutic use; D054328:Proton Pump Inhibitors / Q000008:administration & dosage* / Q000627:therapeutic use; D016559:Tacrolimus / Q000627:therapeutic use
chemical_list: D007166:Immunosuppressive Agents; D054328:Proton Pump Inhibitors; D003404:Creatinine; D009173:Mycophenolic Acid; D011241:Prednisone; D016559:Tacrolimus