Clinical applicability of 2023 International Pediatric Nephrology Association recommended limited therapeutic drug monitoring formulae to assess mycophenolic acid exposure.

Abstract

Background: The 2023 IPNA guidelines recommended a 12-h mycophenolic acid (MPA) area under the curve (AUC) estimation for managing pediatric nephrotic syndrome and MPA AUC > 50 mg * h/L for an optimal therapeutic response to mycophenolate mofetil (MMF). The IPNA guidelines endorsed two limited AUC formulae based on three-point MPA measurements to predict 12-h MPA AUC. The relative performance of these two limited AUC formulae has not been tested.

Methods: We analyzed 156 MPA AUCs from 122 stable kidney transplant recipients to predict the 12-h AUC (10 MPA measurements analyzed with trapezoid rule) using the IPNA-recommended three-point Formula 1 and Formula 2.

Results: Three-point Formula 1 and Formula 2 classified 69% and 60% limited MPA AUCs as > 50 mg * h/L (difference 8.90%, p = 0.10). Three-point Formula 1 and Formula 2 demonstrated a similar association with 12-h AUC (R² 0.72 vs. 0.71) and exhibited identical areas under ROC (AUROC) for predicting 12-h AUC > 50 mg * h/L (AUROC 0.82, 95% CI 0.75, 0.88 vs. 0.80, 95% CI 0.73, 0.86; p = 0.53). Fixed MMF dose and MPA C0 level showed a relatively weaker association (R² 0.16 and 0.43) with 12-h AUC. Four-point MPA formulae improved the prediction of 12-h AUC compared to the three-point formulae. Among all C0 thresholds, C0 > 3.5 mg/L demonstrated the best prediction of 12-h AUC > 50 mg * h/L (AUROC 0.74, 95% CI 0.66, 0.80).

Conclusions: IPNA recommended limited AUC formulae perform equivalently and improve upon MMF dose and C0 level to predict 12-h MPA AUC.