Mycophenolic acid therapeutic drug monitoring using area under the curve in pediatric heart transplant recipients

Abstract

IntroductionPharmacokinetics of mycophenolic acid (MPA) display substantial interpatient variability, with up to 10‐fold difference of exposure in individual patients under a fixed‐dose regimen. MPA trough level (C0) monitoring is common in clinical practice but has not proven sufficiently informative in predicting MPA exposure or patient outcomes, especially in children. No limited sampling strategies (LSSs) have been generated from pediatric heart transplant (HTx) recipients to estimate MPA AUC.MethodsSingle‐center, observational analysis of 135 de novo pediatric HTx recipients ≤21 years old who underwent MPA AUC between 2011 and 2021.ResultsMedian age was 4 years (IQR .6–12.1). Median time from transplant to MPA AUC sampling was 15 days (IQR 11–19). MMF doses (mg or mg/day) had low, negative Pearson correlation coefficients (r) while doses adjusted for weight or body surface area had low correlation with Trapezoidal MPA AUC0–24 h (r = .3 and .383, respectively). MPA C0 had weak association (r = .451) with Trapezoidal MPA AUC0–24 h. LSS with two pharmacokinetic sampling time points at 90 (C3) and 360 (C5) min after MMF administration (estimated AUC0–24 h = 32.82 + 4.12 × C3 + 11.53 × C5) showed strong correlation with Trapezoidal MPA AUC0–24 h (r = .87).ConclusionMMF at fixed or weight‐adjusted doses, as well as MPA trough levels, correlate poorly with MPA AUC0–24 h. We developed novel LSSs to estimate Trapezoidal MPA AUC from a large cohort of pediatric HTx recipients. Validation of our LSSs should be completed in a separate cohort of pediatric HTx recipients.

Prevalence of iron deficiency and anemia in pediatric heart transplant recipients

“…One hypothetical explanation is that MPA is known to have significant gastrointestinal side effects and perhaps compromised absorption of enteral iron intake. 27 In children, normal eGFR is considered greater than 90 mL/min/1.73 m 2 while CKD is defined by an eGFR < 75 mL/min/1.73 m 2 . 28 Primary contributing factors of anemia in children with decreased kidney function can be from endogenous erythropoietin deficiency and iron deficiency.…”