Effects of gastric emptying on oral mycophenolic acid pharmacokinetics in stable renal allograft recipients

Aim To investigate the effect of gastric emptying on the pharmacokinetics of mycophenolic acid (MPA) in renal transplant patients. Methods We assessed the effect of gastric emptying on the disposition of MPA in 27 stable renal allograft recipients at 2 years after transplantation. Gastric emptying was measured by the C-14-octanoate and C-13-glycine breath test. Results Delayed gastric emptying was associated with a significantly longer MPA t(max) [1.0 (0.33-2.0) h vs. 0.5 (0.33-1.0) h; mean difference 0.39 h, 95% confidence interval (CI) 0.03, 0.75; P = 0.0289] and with a significant decrease in the maximum MPA concentration after dosing [10.6 (6.5-21.3) mg l(-1)vs. 20.1 (10.7-28.5) mg l(-1); mean difference 6.5 mg l(-1), 95% CI 2.1, 10.9; P = 0.0075]. Despite the substantial effect of delayed gastric emptying rates on MPA C-max and t(max), total dose-interval exposure, measured by the MPA AUC(0-4), was not affected by the rate of gastric emptying [20.4 (13.9-43.0) mg h(-1) l(-1)vs. 22.4 (13.1-29.8) mg h(-1) l(-1)]. Conclusion Delayed gastric emptying was associated with a slower absorption of MPA, a longer time to reach peak concentrations and lower maximum concentrations. These effects should be taken into account when validating limited (< 2 h) sampling strategies to estimate total MPA exposure, which could be unreliable when monitoring patients with gastric emptying disorders.