title: Diminished mycophenolic acid exposure caused by omeprazole may be clinically relevant in the first week posttransplantation.
abstract: BACKGROUND
  Some studies have reported a decreased absorption of mycophenolic acid (MPA) from mycophenolate mofetil (MMF) in renal transplanted (RTx) patients under proton-pump inhibitors (PPIs). There is still a lack of information regarding (1) whether this effect occurs when MMF is administered with either tacrolimus or cyclosporine A [calcineurin inhibitors (CNIs)], (2) whether the effect has the same amplitude during the first year after RTx, and finally (3) whether this decrease in exposure is clinically relevant.
  
  
  METHODS
  We retrospectively analyzed the omeprazole effect in 348 12-hour pharmacokinetic samplings [area under the curve (AUC)(0-12h)] performed on days 7, 14, 30, 60, 180, and 360 after RTx in 77 patients who participated in previous trials.
  
  
  RESULTS
  For all periods, the groups with and without PPI did not differ in all variables. By mixed-model analysis of variance, PPI reduced the MPA AUC(0-12h) (P < 0.0008) in the patients under both CNIs mainly due to decreased absorption (P = 0.049). In the tacrolimus group, a lower exposure seemed also due to a decreased MPA reabsorption at 10-12 hours. The PPI effect remains throughout the first year but was clinically more important on day 7. By Cox analysis, the use of PPI was associated with a 25% less chance of being adequately exposed to MPA (95% confidence interval 0.58-0.99, P = 0.04). Similarly, the number of patients underexposed to MPA (AUC < 30 ng·h/mL) was higher at most periods in the PPI group but again not statistically significant.
  
  
  CONCLUSIONS
  These data indicate that PPI decreases the MPA exposure when associated with both CNIs but particularly in the first week after RTx. In this period, the MMF dose should be increased. This effect lasts throughout the first year but does not seem to be clinically relevant after the first week.
authors.affiliation: Division of Urology, Renal Transplantation Service, University of Sao Paulo, Sao Paulo, Brazil. elias.david.neto@attglobal.net
authors.forename: Elias
authors.initials: E
authors.lastname: David-Neto
authors.forename: Kelly M
authors.initials: KM
authors.lastname: Takaki
authors.forename: Fabiana
authors.initials: F
authors.lastname: Agena
authors.forename: Paschoalina
authors.initials: P
authors.lastname: Romano
authors.forename: Nairo M
authors.initials: NM
authors.lastname: Sumita
authors.forename: Maria E
authors.initials: ME
authors.lastname: Mendes
authors.forename: Leticia Aparecida Lopes
authors.initials: LA
authors.lastname: Neri
authors.forename: William C
authors.initials: WC
authors.lastname: Nahas
mesh_terms: D000328:Adult; D004347:Drug Interactions / Q000502:physiology; D005260:Female; D006801:Humans; D016030:Kidney Transplantation / Q000502:physiology*; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000008:administration & dosage / Q000097:blood*; D009853:Omeprazole / Q000008:administration & dosage / Q000097:blood*; D054328:Proton Pump Inhibitors / Q000008:administration & dosage / Q000097:blood; D012189:Retrospective Studies; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D054328:Proton Pump Inhibitors; D009173:Mycophenolic Acid; D009853:Omeprazole