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High-unbound mycophenolic acid concentrations in an infant on peritoneal dialysis following hematopoietic cell transplant

Bone Marrow Transplantation volume 40, pages 911–912 (2007)Cite this article

Mycophenolic acid (MPA) is a prodrug of the immune suppressant mycophenolate mofetil (MMF). MMF is hydrolyzed to MPA after oral and i.v. administration. It is metabolized further by glucuronosyltransferase enzymes to form the primary metabolite MPA 7-O-glucuronide (MPAG) and the minor metabolite acyl MPA glucuronide (AcMPAG). MPA and MPAG are extensively bound to albumin, 97–99 and 85%, respectively. Only unbound MPA is pharmacologically active. MPAG and AcMPAG are renally excreted and accumulate in renal dysfunction. Because clinical events may lead to the altered binding of MPA to albumin, assessment of systemic exposure based on total MPA concentrations alone may be misleading.

A 7 month-old female infant with high risk, bilineage acute leukemia [t(11;19)] was admitted to the University of Minnesota for hematopoietic cell transplant (HCT). She received a myeloablative preparatory regimen of BU, melphalan and fludarabine. Immunosuppression was with MMF 110 mg (15.5 mg kg−1) every 8 h i.v. and CY 15 mg every 8 h i.v. beginning on day −3. Her pretransplant labs were blood urea nitrogen 3 mg dl−1, Cr 0.16 mg dl−1, total bilirubin 0.2 mg dl−1 and albumin 4.1 g dl−1 and weight was 7.1 kg. By day 4 her weight had increased by 1.8 kg and Cr to 0.7 mg dl−1. On day 0 she received an unrelated, partially matched double umbilical cord blood transplant. She was emergently intubated after the infusion secondary to acute hypoxia and pulmonary edema. She subsequently developed mild hepatic veno-occlusive disease although her bilirubin and liver enzymes increases only modestly.

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Authors and Affiliations

  1. Department of Experimental and Clinical Pharmacology, College of Pharmacy, University of Minnesota, Minneapolis, MN, USA

    P A Jacobson & J Huang

  2. University of Minnesota Cancer Center, Minneapolis, MN, USA

    P A Jacobson

  3. Department of Pharmacy, Fairview University Medical Center, Minneapolis, MN, USA

    N Rydhom

  4. Department of Pediatrics, Division of Pediatric Hematology, Oncology and Transplantation, University of Minnesota, School of Medicine, Minneapolis, MN, USA

    K S Baker & M R Verneris

  5. Blood and Marrow Transplant Program, University of Minnesota, School of Medicine, Minneapolis, MN, USA

    K S Baker & M R Verneris

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  1. P A Jacobson
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Correspondence to P A Jacobson.

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Jacobson, P., Rydhom, N., Huang, J. et al. High-unbound mycophenolic acid concentrations in an infant on peritoneal dialysis following hematopoietic cell transplant. Bone Marrow Transplant 40, 911–912 (2007). https://doi.org/10.1038/sj.bmt.1705837

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