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Developmental changes of MPA exposure in children
Elisa C Yoo1, Ana Catalina Alvarez-Elías1,2, Ekaterina Kirilova Todorova1
1Department of Pediatrics, Schulich School of Medicine & Dentistry, London, ON, Canada, N6A 5W9.
Background:
Developmental changes (ontogeny) of drug disposition of Mycophenolate mofetil (MMF) have been understudied.
Methods:
The charts of 37 pediatric renal transplant recipients (median age 7.3 years, median follow-up 7.8 (IQR 6.6, 14.3 years) who had regular mycophenolic acid (MPA) trough level monitoring in combination with tacrolimus (n = 31) or sirolimus (n = 6) therapy were analyzed retrospectively for their dose-normalized MPA exposure, steroid dose, albumin, hematocrit, and cystatin C estimated glomerular filtration rate (eGFR). Using appropriate univariate and multivariate methods, we determined whether MPA exposure was age dependent when controlling for the confounders.
Results:
Dose-normalized MPA trough levels could be calculated in 2,128 (median 45/patient) instances. Spearman rank correlation analysis revealed that age correlated with dose-normalized MPA trough level for both body weight and body surface area, as well as serum albumin, hematocrit, steroid dose, and eGFR. In the multivariate analysis, serum albumin and steroid dose were not significant, and hematocrit only being significant when the youngest group of patients < 6 years of age was compared. eGFR was the most important confounder, but age dependency remained significant when controlling for all confounders.
Conclusions:
Small children are at a significantly greater risk for low MPA trough levels than adolescents, highlighting the need for pharmacokinetic monitoring of MPA.
Insights
Pediatric renal transplant patients, especially those younger than 6 years, face a higher risk of low mycophenolic acid (MPA) levels. This underscores the critical need for pharmacokinetic monitoring of MPA in children.
Area of Science:
- Pharmacology
- Pediatric Nephrology
- Transplantation
Background:
- Developmental changes in Mycophenolate mofetil (MMF) drug disposition are not well understood.
- MMF is a crucial immunosuppressant in pediatric renal transplant recipients.
Purpose of the Study:
- To investigate the age-dependency of mycophenolic acid (MPA) exposure in pediatric renal transplant recipients.
- To identify factors influencing MPA trough levels in this population.
Main Methods:
- Retrospective analysis of 37 pediatric renal transplant recipients.
- Monitoring of dose-normalized MPA trough levels, along with clinical parameters like albumin, hematocrit, and eGFR.
- Univariate and multivariate analyses to assess age dependency while controlling for confounders.
Main Results:
- Age significantly correlated with dose-normalized MPA trough levels.
- Estimated glomerular filtration rate (eGFR) was a key confounder, but age dependency remained significant.
- Younger children (< 6 years) showed a greater risk for low MPA trough levels compared to adolescents.
Conclusions:
- Significant age-related differences in MPA exposure exist in pediatric renal transplant recipients.
- Pharmacokinetic monitoring of MPA is essential, particularly in younger children, to ensure therapeutic efficacy and safety.
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