Diminished mycophenolic acid exposure caused by omeprazole may be clinically relevant in the first week posttransplantation.

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.

The need of mycophenolic acid monitoring in long-term renal transplants.

BACKGROUND: There is little information regarding the 12-h mycophenolic acid (MPA) pharmacokinetics (PK), a way to monitor the drug and the need of frequent monitoring, in stable patients. METHODS: A cohort of 35 adults, under long-term mycophenolate mofetil (MMF) therapy plus cyclosporin A (n = 12), TACimus (n = 12) or MMF only (n = 11); all with prednisone had a 12-h MPA-PK performed to ascertain the percentage of them within a defined therapeutic window. In 13 other patients, two PK studies undergone 1 wk apart were performed to evaluate the need for frequent measurements. RESULTS: Fourteen (40%) patients were within the defined therapeutic window (36-60 microg h/mL). Nine patients (26%) were overexposed while 12 (34%) were underexposed. A Cmax> or =10 microg/mL was seen in 20 (57%) of the patients. These percentages were equally distributed between the treatment groups both for AUC0-12 and Cmax. The equations using C0, C2 or both predict exposure, although the use of C2 seems to be more adequate in clinical practice. There were no differences in MPA exposure in patients with a repeated PK evaluated 1 wk later. CONCLUSION: The use of MMF without monitoring MPA blood levels may cause over-/underexposure to the drug in stable recipients. However, in patients under MMF for more than 1 yr, MPA levels are stable and there is no need for frequent measurements.