title: Developmental changes of MPA exposure in children.
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.
authors.affiliation: Department of Pediatrics, Schulich School of Medicine & Dentistry, London, ON, Canada, N6A 5W9.
authors.forename: Elisa C
authors.initials: EC
authors.lastname: Yoo
authors.affiliation: Department of Pediatrics, Schulich School of Medicine & Dentistry, London, ON, Canada, N6A 5W9.|Universidad Nacional Autónoma de México, Mexico City, Mexico, 04510.
authors.forename: Ana Catalina
authors.initials: AC
authors.lastname: Alvarez-Elías
authors.affiliation: Department of Pediatrics, Schulich School of Medicine & Dentistry, London, ON, Canada, N6A 5W9.
authors.forename: Ekaterina Kirilova
authors.initials: EK
authors.lastname: Todorova
authors.affiliation: Department of Pediatrics, Schulich School of Medicine & Dentistry, London, ON, Canada, N6A 5W9. guido.filler@lhsc.on.ca.|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.|Department of Medicine, Schulich School of Medicine & Dentistry, University of Western Ontario, London, ON, Canada, 5A 5A5. guido.filler@lhsc.on.ca.|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.
authors.forename: Guido
authors.initials: G
authors.lastname: Filler
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D002648:Child; D002657:Child Development; D002675:Child, Preschool; D016903:Drug Monitoring; D004359:Drug Therapy, Combination; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics*; D005260:Female; D005500:Follow-Up Studies; D005919:Glomerular Filtration Rate; D006084:Graft Rejection / Q000188:drug therapy; D006801:Humans; D007168:IMP Dehydrogenase / Q000037:antagonists & inhibitors*; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D016030:Kidney Transplantation; D008297:Male; D009173:Mycophenolic Acid / Q000493:pharmacokinetics* / Q000627:therapeutic use; D051436:Renal Insufficiency, Chronic / Q000601:surgery; D012189:Retrospective Studies; D020123:Sirolimus / Q000627:therapeutic use; D016559:Tacrolimus / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D004791:Enzyme Inhibitors; D007166:Immunosuppressive Agents; D007168:IMP Dehydrogenase; D009173:Mycophenolic Acid; D020123:Sirolimus; D016559:Tacrolimus
keywords: Kidney transplantation; Mycophenolate mofetil; Mycophenolic acid trough levels; Ontogeny; Pediatric; Therapeutic drug monitoring