Pharmacokinetics-based optimal dose prediction of donor source-dependent response to mycophenolate mofetil in unrelated hematopoietic cell transplantation.

Abstract	Mycophenolate mofetil (MMF) has been widely used for prophylaxis against graft-versus-host disease (GVHD) following allogeneic hematopoietic stem cell transplantation (allo-SCT). However, no clear advantage over methotrexate has been reported, other than reduced incidence of mucositis. We speculated that the wide inter-individual variation of plasma mycophenolic acid (MPA) levels veiled the benefits of MMF. Data from 36 unrelated allogeneic bone marrow (allo-BMT) and cord blood transplantation (CBT) were analyzed retrospectively based on MPA area under the curve (AUC(0-24h)). In allo-BMT, high AUC(0-24h) (>30 μg h/ml) resulted in no incidence of grade II-IV acute/extensive chronic GVHD and tended to show higher overall and disease-free survival, lower relapse rates, and non-relapse mortality. In CBT, AUC(0-24h) less than 30 μg h/ml was sufficient for low incidence of acute/chronic GVHD and high survival. Strong correlation between AUC(0-24h) and C(2h), plasma MPA concentration at 2 h after administration was observed. Single point assessment of C(2h) was shown to provide a useful surrogate of AUC(0-24h) to predict GVHD incidence. The results of this study suggest that individualized MMF dosing in a donor source-dependent fashion may be important for maximizing the benefit of MMF in allo-SCT.
Authors	Kanako Wakahashi, Motohiro Yamamori, Kentaro Minagawa, Shinichi Ishii, Shinichirou Nishikawa, Manabu Shimoyama, Hiroki Kawano, Yuko Kawano, Yuriko Kawamori, Akiko Sada, Toshimitsu Matsui, Yoshio Katayama
Journal	International journal of hematology (Int J Hematol) Vol. 94 Issue 2 Pg. 193-202 (Aug 2011) ISSN: 1865-3774 [Electronic] Japan
PMID	21751082 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	Antineoplastic Agents Mycophenolic Acid
Topics	Adult Aged Antineoplastic Agents Area Under Curve Dose-Response Relationship, Drug Drug Dosage Calculations Female Graft vs Host Disease (prevention & control) Hematopoietic Stem Cell Transplantation (adverse effects, methods) Humans Middle Aged Mycophenolic Acid (administration & dosage, analogs & derivatives, pharmacokinetics) Pharmacokinetics Retrospective Studies Tissue Donors Treatment Outcome Young Adult

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