title: Pharmacokinetics-based optimal dose-exploration of mycophenolate mofetil in allogeneic hematopoietic stem cell transplantation.
abstract: For better clinical outcomes of mycophenolate mofetil (MMF) in allogeneic hematopoietic stem cell transplantation (alloSCT), higher mycophenolic acid (MPA) plasma levels are proposed to be desirable. Here, we investigate the optimal MMF dosing strategy based on pharmacokinetic studies in 20 Japanese alloSCT patients. The first 11 patients received MMF twice daily at an escalated dose from 15 mg/kg, according to real-time pharmacokinetic monitoring of the total MPA area under the curve (AUC). In the subsequent nine patients, MMF was given at a fixed dose of 1,000 mg three-times daily. The pharmacokinetic data revealed that the dose escalation in each individual did not always increase the AUC. In contrast, the increase of dosing frequency could statistically keep higher MPA plasma levels, as reflected in higher concentration at steady state (C (ss)) or trough value (C (trough)). There was no symptomatic adverse event in both groups. These results suggest that MMF administration of every 8 h after alloSCT would be better to maintain higher MPA plasma levels than that of every 12 h even in the same daily dose. Further studies are necessary to confirm the clinical benefit of MMF to prevent graft failure, as well as severe aGVHD.
authors.affiliation: Hematology/Oncology, Department of Medicine, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan.
authors.forename: Atsuo
authors.initials: A
authors.lastname: Okamura
authors.affiliation: Department of Hospital Pharmacy, Kobe University Hospital, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan.
authors.forename: Motohiro
authors.initials: M
authors.lastname: Yamamori
authors.affiliation: Hematology/Oncology, Department of Medicine, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan.
authors.forename: Manabu
authors.initials: M
authors.lastname: Shimoyama
authors.affiliation: Hematology/Oncology, Department of Medicine, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Kawano
authors.affiliation: Hematology/Oncology, Department of Medicine, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Kawano
authors.affiliation: Hematology/Oncology, Department of Medicine, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan.
authors.forename: Yuriko
authors.initials: Y
authors.lastname: Kawamori
authors.affiliation: Hematology/Oncology, Department of Medicine, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan.
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Nishikawa
authors.affiliation: Hematology/Oncology, Department of Medicine, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Minagawa
authors.affiliation: Hematology/Oncology, Department of Medicine, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan.
authors.forename: Kimikazu
authors.initials: K
authors.lastname: Yakushijin
authors.affiliation: Hematology/Oncology, Department of Medicine, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan.
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Katayama
authors.affiliation: Department of Hospital Pharmacy, Kobe University Hospital, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan.
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Sakaeda
authors.affiliation: Department of Hospital Pharmacy, Kobe University Hospital, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan.
authors.forename: Midori
authors.initials: M
authors.lastname: Hirai
authors.affiliation: Hematology/Oncology, Department of Medicine, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan. matsui@med.kobe-u.ac.jp.
authors.forename: Toshimitsu
authors.initials: T
authors.lastname: Matsui
mesh_terms: D000208:Acute Disease; D000328:Adult; D000368:Aged; D044466:Asian People; D005260:Female; D006084:Graft Rejection / Q000517:prevention & control*; D006086:Graft vs Host Disease / Q000517:prevention & control*; D019337:Hematologic Neoplasms / Q000628:therapy*; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D036102:Peripheral Blood Stem Cell Transplantation; D014184:Transplantation, Homologous
chemical_list: D007166:Immunosuppressive Agents; D009173:Mycophenolic Acid