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Pediatr Nephrol. 2016 Jun;31(6):975-82. doi: 10.1007/s00467-015-3303-3. Epub 2016 Jan 7.

Developmental changes of MPA exposure in children.

Author information

1
Department of Pediatrics, Schulich School of Medicine & Dentistry, London, ON, Canada, N6A 5W9.
2
Universidad Nacional Autónoma de México, Mexico City, Mexico, 04510.
3
Department of Pediatrics, Schulich School of Medicine & Dentistry, London, ON, Canada, N6A 5W9. guido.filler@lhsc.on.ca.
4
Department of Pathology and Laboratory Medicine, Schulich School of Medicine & Dentistry, University of Western Ontario, London, Ontario, Canada, N5A 5A5. guido.filler@lhsc.on.ca.
5
Department of Medicine, Schulich School of Medicine & Dentistry, University of Western Ontario, London, ON, Canada, 5A 5A5. guido.filler@lhsc.on.ca.
6
Department of Pediatrics, Children's Hospital, London Health Sciences Centre, University of Western Ontario, 800 Commissioners Road East, London, ON, Canada, N6A 5W9. guido.filler@lhsc.on.ca.

Abstract

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.

KEYWORDS:

Kidney transplantation; Mycophenolate mofetil; Mycophenolic acid trough levels; Ontogeny; Pediatric; Therapeutic drug monitoring

PMID:
26743220
DOI:
10.1007/s00467-015-3303-3
[Indexed for MEDLINE]

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