Pharmacokinetics and abbreviated AUC model of enteric-coated mycophenolate sodium in early kidney transplant recipients receiving tacrolimus

Enteric-coated mycophenolate sodium (EC-MPS) is used in kidney transplant recipients (KTRs) as an alternative to mycophenolate mofetil for improved gastrointestinal tolerability. However, its variable absorption complicates therapeutic drug monitoring (TDM), and pharmacokinetic data in the early post-transplant period remain limited. In this single-center, open-label pharmacokinetic study, 20 kidney transplant recipients (KTRs) receiving EC-MPS with tacrolimus underwent 12-h plasma mycophenolic acid (MPA) concentration profiling on day 3 post-transplantation. The full area under the curve (AUC₀₋₁₂) was calculated using the trapezoidal method. Correlations between single-timepoint concentrations and AUC were assessed, and abbreviated AUC models were developed using linear regression. Clinical outcomes were followed for 6 months. The geometric mean AUC₀₋₁₂ was 37.06 mg h/L (coefficient of variation 42.5%), with 25% of patients underexposed (< 30 mg h/L). No single time point demonstrated a strong correlation with AUC₀₋₁₂ (maximum R² = 0.386 at 4 h), confirming the inadequacy of trough or single-point monitoring. The best-performing abbreviated model incorporated C1, C4, and C10 (R² = 0.844). A simplified three-point model using C1.5, C3.5, and C6 also yielded acceptable predictive accuracy (R² = 0.721). Patients with low AUC₀₋₁₂ exhibited significantly higher serum creatinine on day 3 and increased graft failure risk at 6 months (p = 0.036), underscoring the clinical impact of underexposure. When comparing baseline characteristics, patients in the underexposed group had significantly higher body weight (70.4 vs. 56.5 kg, p = 0.021) and higher day-3 serum creatinine (11.2 vs. 5.3 mg/dL, p = 0.037). EC-MPS shows substantial pharmacokinetics variability in early post-transplant KTRs, and single time-point monitoring is inadequate for estimating MPA exposure. A practical three-point abbreviated AUC model provides accurate estimation and may improve TDM in tacrolimus-treated recipients. Validation in larger, more diverse cohorts is warranted.