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

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.