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 AUC0-6h were 1.8 ± 1.2 mg/L and 31.1 ± 14.8 mg*h/L, respectively. The dose-corrected AUC0-6h was 35.4 ± 17.9 mg*h/L. Regarding the single time points, C0 showed a low correlation with AUC0-6h (r2 = .34); C1.5, 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 AUC0-6 (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. © 2007 Elsevier Inc. All rights reserved.