Drug–Drug Interactions Between Mycophenolic Acid and Proton Pump Inhibitors: A Systematic Review and Meta-Analysis

Purpose: The objective of the present study was to determine the impact of proton pump inhibitors (PPIs) on the pharmacokinetics and pharmacodynamics of mycophenolic acid (MPA). Methods: PubMed, Embase, Web of Sciences, and Scopus were systematically searched to identify relevant studies reporting pharmacokinetic parameters [including trough concentration (C 0 ), maximum concentration (C max ), time to maximum concentration (T max ), the dose-adjusted area under the concentration–time curve from time 0–12 hours (AUC 0–12 h /D), and half-life (t 1/2 )], and pharmacodynamic outcomes of MPA (eg, acute graft rejection and adverse drug reactions), with and without PPI administration. Pooled effect estimates were calculated using a random-effects model. Results: Twelve studies involving 473 participants were eligible for inclusion, 11 of which were included in the meta-analysis. PPI exposure was significantly associated with lower C 0 [mean difference (MD) = −0.62 mg/L; P = 0.003] lower C max (MD = −4.71 mg/L; P = 0.01), and longer T max (MD = 0.30 hours; P = 0.0001) of MPA. However, no significant association was observed between PPI exposure and AUC 0–12 h /D, t 1/2 , or any pharmacodynamic outcomes. Based on subgroup analysis, it can be suggested that a significant association between PPI exposure and altered MPA pharmacokinetics was mainly associated with mycophenolate mofetil but not enteric-coated mycophenolate sodium. Conclusions: Coadministration of PPIs and mycophenolate mofetil significantly altered the pharmacokinetics of MPA, particularly by decreasing MPA absorption. However, PPI-MPA interactions did not impact pharmacodynamic outcomes of MPA.