Race and drug formulation influence on mycophenolic acid pharmacokinetics in stable renal transplant recipients

Background: Limited mycophenolic acid (MPA) data are available comparing racial influence on mycophenolate mofetil (MMF) and enteric-coated mycophenolate sodium (EC-MPS) pharmacokinetics. Methods: Intrapatient MPA pharmacokinetics of MMF versus EC-MPS were compared in 13 male African American (AA) and 14 Caucasian (C) renal transplant recipients (RTRs). RTRs were switched to equivalent doses of the alternate formulation for at least 10 days prior to the second study. Mycophenolic acid clearance and dose-normalized area under the concentration-time curve 0-12 (AUC) were determined. Mixed model statistics evaluated the main effects of race, drug formulation, and interaction of race and drug formulation (R×D) with albumin, cyclosporine trough, renal function, and diabetes and enterhepatic recirculation. Results: Significant R×D was identified for MPA AUC for EC-MPS (AA, 0.056 ± 0.029 [mg.h/L]/mg; C, 0.080 ± 0.044 [mg.h/L]/mg) compared with MMF (AA, 0.053 ± 0.019 [mg.h/L]/mg; C, 0.060 ± 0.025 [mg.h/L]/mg), P = .022. Significant R×D was identified with albumin in the model for MPA clearance for MMF (AA, 21.7 ± 8.9 L/h; C, 20.5 ± 10.8 L/h) compared with EC-MPS (AA, 22.2 ± 10.1 L/h; C, 16.2 ± 9.1 L/h), P = .032. Conclusions: Race influences MPA exposure between MMF and EC-MPS and may warrant therapeutic monitoring during formulation conversion.