Therapeutic Drug Monitoring of Mycophenolic Acid in Kidney Transplant Patients: A Abbreviated Sampling Strategy

Abstract 

Mycophenolic acid (MPA) levels have demonstrated a good correlation with clinical outcomes, but with great pharmacokinetic variability between patients. Therapeutic drug monitoring (TDM) is recommended to include a 12-hour area under the concentration–time curve (AUC). Since full AUC estimates are not practical for routine monitoring, limited sampling strategies have been suggested. We evaluated MPA pharmacokinetics in 18 stable renal transplant patients receiving mycophenolate mofetil (MMF) as part of their immunosuppressive therapy. The correlation between measured and estimated AUC was assessed using 4 different sparse sampling algorithms. The mean values for C₀ and AUC_0–6h were 1.8 ± 1.2 mg/L and 31.1 ± 14.8 mg*h/L, respectively. The dose-corrected AUC_0–6h was 35.4 ± 17.9 mg*h/L. Regarding the single time points, C₀ showed a low correlation with AUC_0–6h (r² = .34); C_1.5, the best correlation (r² = .72); and C₃, the worst (r² = .07). Sparse sample algorithms used to estimate 12-hour AUC including C₀, C₁, C₂, C₃, C₄, and/or C₆ showed a good correlation with the calculated AUC_0–6 (r² = .81–.96). The algorithm that used C₀, C₁, C₂, and C₄ showed the best correlation, but we also found a good correlation (r² = .91) with C₀, C₁, and C₂. Based on these results, we have suggested using the 3-point algorithm (C₀, C₁, and C₂) for MPA TDM in stable renal transplant patients due to the good correlation with drug exposure and better functionality than an algorithm using a 4-hour postdose measurement.