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Pharmacokinetics of mycophenolate mofetil in hematopoietic stem cell transplant recipients

Reinier M van Hest1, Jeanette K Doorduijn, Brenda C M de Winter

  • 1Department of Hospital Pharmacy (Clinical Pharmacology Unit), Erasmus MC, Rotterdam, The Netherlands. r.vanhest@erasmusmc.nl

Therapeutic Drug Monitoring
|May 29, 2007
PubMed

Insights

Mycophenolate mofetil (MMF) pharmacokinetics in hematopoietic stem cell transplant (HCT) recipients show low drug exposure and short half-life. Dosing adjustments may be needed to improve mycophenolic acid (MPA) levels for graft-versus-host disease (GVHD) prophylaxis.

Area of Science:

  • Pharmacology
  • Transplantation Medicine
  • Immunosuppression

Background:

  • Mycophenolate mofetil (MMF) is an immunosuppressant used for graft-versus-host disease (GVHD) prophylaxis post-hematopoietic stem cell transplantation (HCT).
  • Limited pharmacokinetic data exist for MMF in HCT recipients.

Purpose of the Study:

  • To analyze the pharmacokinetics of MMF in HCT recipients.
  • To evaluate total and free mycophenolic acid (MPA) plasma concentrations.
  • To provide data for optimizing MMF dosing in HCT.

Main Methods:

  • Case series of 15 HCT recipients receiving twice-daily oral MMF.
  • Serial plasma sampling to quantify total MPA, MPA glucuronide metabolites, and free MPA.
  • Pharmacokinetic parameters including clearance (CL/F), half-life, and area under the curve (AUC0-12) were calculated.

Main Results:

  • Median apparent oral MPA clearance (CL/F) was 56 L/h, with a short half-life of 2.3 hours.
  • Total MPA exposure (AUC0-12) was 18.0 mg*h/L, and free MPA AUC0-12 was 224 microg*h/L.
  • Low total MPA concentrations (<2 mg/L at 8 hours) suggest reduced enterohepatic recirculation.

Conclusions:

  • HCT recipients exhibit high MPA clearance and short half-life compared to renal transplant patients.
  • Current MMF dosing may result in suboptimal MPA exposure for GVHD prophylaxis in HCT.
  • Increased MMF dosage or frequency could potentially improve MPA exposure and therapeutic outcomes.

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