Impact of Omeprazole On Mycophenolic Acid Pharmacokinetics in Adult Renal Transplant Patients.

Abstract

Background:Published studies have shown that proton pump inhibitors(PPIs) reduce the mycophenolic acid(MPA) area-under-the-curve(AUC0-12) in patients treated with mycophenolate mofetil(MMF), but not with enteric-coated mycophenolate sodium(EC-MPS). Aim:To analyse the impact of omeprazole(OME) coadministration on MPA pharmacokinetics in adult renal transplant patients treated with MMF(Cellcept®) or EC-MPS(Myfortic®). Patients and methods:Crossover study of 20 patients who underwent a cadaveric renal transplantation, in a stable clinical situation (6th month post-transplant), with tacrolimus, prednisone and MPA equivalent doses (500 mg MMF˜360 mg EC-MPS) and a 20-mg OME daily dose administered in the morning around 30 minutes before immunosuppressive therapy. For each patient, two pharmacokinetic profiles were obtained with OME treatment (1st) and without OME treatment (2nd), with a 7-10-day washout period between each. Samples were extracted before and at 1,2,3,4,6 and 8h after the oral MMF or EC-MPS morning dose. Plasma levels were measured using EMIT on Dimension™analyser. AUC0-12 was calculated using linear trapezoidal rule. MPA trough levels (Ctrough) and AUC0-12 valueswere compared during and after OME discontinuation. Statistical analysis: SPSS version 19.0. Wilcoxon Signed Rank Test was used for studying Ctrough and AUC0-12 variations. P<0.05: statistically significant. Results:The study included 20 patients (9:MMF, 11:EC-MPS), mean age: 50 years, mean weight: 69 kg.In patients treated with MMF, pharmacokinetic variables for those receiving OME or not were respectively: Ctrough (3.12±1.58 vs. 1.96±0.85 ng/mL,p=0.021, median 2.50 vs. 1.80) and AUC0-12 (49.34±10.47 vs. 37.37±7.68 ng.h/mL, p=0.008, median 50.25 vs. 38.85). When the patients were treated with EC-MPS, these parameters were:Ctrough (4.54±4.03 vs. 4.12±2.78 ng/mL,p=0.878, median 2.80 vs. 3.10) and AUC0-12 (52.04±39.78 vs. 71.87±43.03 ng.h/mL, p=0.003,median 41.55 vs.54.25). Conclusions: As omeprazole is an inhibitor, this study performed on renal transplant patients showed a significantly higher exposure (AUC0-12)with OME comedication during MMF and EC-MPS therapy. With respect to Ctrough, OME increased the obtained value for patients treated with MMF but not with EC-MPS.