Real-World Pharmacokinetics of Mycophenolic Acid and Comparison of Exposure from Young Children to Young Adults

Objectives: Mycophenolate mofetil (MMF) is an immunosuppressant with complex pharmacokinetics (PK) used in pediatric transplant recipients. Therapeutic drug monitoring (TDM) of its active metabolite, mycophenolic acid (MPA), is recommended. Assessment of MPA exposure based on the area under the concentration–time curve (AUC) is challenging due to limited sampling strategies. This study aimed to characterize MPA PK across a broad pediatric age range and to examine MPA AUC0–12h estimated by MwPharm++, a clinical pharmacokinetic software tool used for model-informed therapeutic drug monitoring and individualized dosing. Methods: This retrospective single-center observational study collected steady state MPA levels at trough, 30 and 120 min. A population pharmacokinetic (popPK) approach (NONMEM) was used to characterize MPA PK. AUC0–12h was first estimated by MwPharm++ and then compared with AUC0–12h based on NONMEM post hoc estimates. Results: A total of 1368 MPA concentrations from 456 TDM occasions in 169 patients (infants: 0–≤ 2 years, n = 3; young children: > 2–≤ 5 years, n = 47; older children: > 5–≤12 years, n = 193; adolescents: > 12–≤ 17 years, n = 117; young adults: > 17–24 years, n = 96) were described by a two-compartment model with first-order absorption. After standard allometric scaling based on body weight, albumin and estimated glomerular filtration rate (but not age) significantly influenced apparent clearance (CL/F). Median CL/F was about 45.4% lower in young children compared with adolescents, while median AUC0–12h was similar across age groups from 2 to 24 years, taking into account that doses differed between patients, were initially based on BSA, and may have been adjusted according to previous TDM results or the clinical situation of the patient. AUC0–12h estimates were on average 8.59 mg·h/L higher with NONMEM than with MwPharm++. Conclusions: These findings suggest that allometric scaling captures body weight-related MPA PK changes across age groups in real-world data and support the use of simple pediatric popPK models for exposure assessment.