Highly variable mycophenolate mofetil bioavailability following nonmyeloablative hematopoietic cell transplantation

Pamala Jacobson, Kathleen Green, John Rogosheske, Claudio Brunstein, Breta Ebeling, Todd DeFor, Philip McGlave, Daniel Weisdorf

Research output: Contribution to journalArticlepeer-review

23 Scopus citations

Abstract

This study determined the oral bioavailability of mycophenolic acid, the active metabolite of mycophenolate mofetil, in patients undergoing nonmyeloablative hematopoietic cell transplantation. Eighteen adults receiving a preparative regimen containing fludarabine, cyclophosphamide, and total body irradiation were studied. Immune suppression consisted of cyclosporine and mycophenolate 1 g twice daily. Pharmacokinetic variability was high after intravenous and oral dosing. Intravenous dosing resulted in a median area under the curve (AUC) of 28.3 μg·h/mL (range, 9.96-70.4) and an oral AUC of 16.7 μg·h/mL (range, 9.38-35.3). C max after intravenous and oral dosing was 12.18 and 5.29 μg/mL, respectively. The median oral bioavailability was 72.3% (20.5%-172%), with 8-fold variability. Five patients (28%) had an oral bioavailability ≤50%. At time of oral pharmacokinetics, 15 patients (83%) had an AUC 0-12 <30 μg·h/mL. The initial oral dose should be at least 25% greater than the intravenous dose with follow-up assessment of plasma concentrations.

Original languageEnglish (US)
Pages (from-to)6-12
Number of pages7
JournalJournal of Clinical Pharmacology
Volume47
Issue number1
DOIs
StatePublished - Jan 2007

Keywords

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

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