Higher mycophenolate dose requirements in children undergoing hematopoietic cell transplant (HCT)

Pamala Jacobson, Jaiyin Huang, Nancy Rydholm, Myhang Tran, Todd Defor, Jakub Tolar, Paul J. Orchard

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

Abstract

Little is known about dosing of mycophenolate mofetil in pediatric hematopoietic cell transplant recipients; therefore, dosing strategies using other settings have been extended to this population. The authors studied pharmacokinetics in 19 children (median 17 months) undergoing myeloablative hematopoietic cell transplant and receiving prophylactic mycophenolate and cyclosporine. All subjects except 2 received mycophenolate 15 mg/kg intravenously every 8 hours. The median (range) total mycophenolic acid area under the concentration-time curve (AUC)0-8 was 12.6 mcg·h/ mL (4.9-49.2), and unbound mycophenolic acid AUC0-8 was 0.274 mcg·h/mL (0.037-1.4). Total and unbound mycophenolic acid trough concentrations were 0.27 (0.03-2.9) and 0.005 (0-0.034) mcg/mL, respectively. Mycophenolic acid trough concentrations were not good surrogates for overall exposure (AUC0-8), r2 ≤ 0.55. Mycophenolate dose requirements are higher in pediatric hematopoietic cell transplant recipients relative to pediatric organ transplant recipients. Children undergoing hematopoietic cell transplant should receive a mycophenolate mofetil dose of at least 15 mg/kg intravenously every 8 hours when used in combination with cyclosporine to achieve systemic concentrations near those proposed to be therapeutic in the adult hematopoietic cell transplant population.

Original languageEnglish (US)
Pages (from-to)485-494
Number of pages10
JournalJournal of Clinical Pharmacology
Volume48
Issue number4
DOIs
StatePublished - Apr 2008

Keywords

  • Hematopoietic cell transplantation
  • Mycophenolate mofetil
  • Mycophenolic acid
  • Pediatrics
  • Pharmacokinetics

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