Pharmacokinetics-based optimal dose-exploration of mycophenolate mofetil in allogeneic hematopoietic stem cell transplantation

Atsuo Okamura, Motohiro Yamamori, Manabu Shimoyama, Yuko Kawano, Hiroki Kawano, Yuriko Kawamori, Shinichiro Nishikawa, Kentaro Minagawa, Kimikazu Yakushijin, Yoshio Katayama, Toshiyuki Sakaeda, Midori Hirai, Toshimitsu Matsui

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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.

Original languageEnglish (US)
Pages (from-to)104-110
Number of pages7
JournalInternational journal of hematology
Volume88
Issue number1
DOIs
StatePublished - Jul 1 2008

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Mycophenolic Acid
Hematopoietic Stem Cell Transplantation
Pharmacokinetics
Area Under Curve

All Science Journal Classification (ASJC) codes

  • Hematology

Cite this

Okamura, Atsuo ; Yamamori, Motohiro ; Shimoyama, Manabu ; Kawano, Yuko ; Kawano, Hiroki ; Kawamori, Yuriko ; Nishikawa, Shinichiro ; Minagawa, Kentaro ; Yakushijin, Kimikazu ; Katayama, Yoshio ; Sakaeda, Toshiyuki ; Hirai, Midori ; Matsui, Toshimitsu. / Pharmacokinetics-based optimal dose-exploration of mycophenolate mofetil in allogeneic hematopoietic stem cell transplantation. In: International journal of hematology. 2008 ; Vol. 88, No. 1. pp. 104-110.
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author = "Atsuo Okamura and Motohiro Yamamori and Manabu Shimoyama and Yuko Kawano and Hiroki Kawano and Yuriko Kawamori and Shinichiro Nishikawa and Kentaro Minagawa and Kimikazu Yakushijin and Yoshio Katayama and Toshiyuki Sakaeda and Midori Hirai and Toshimitsu Matsui",
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Okamura, A, Yamamori, M, Shimoyama, M, Kawano, Y, Kawano, H, Kawamori, Y, Nishikawa, S, Minagawa, K, Yakushijin, K, Katayama, Y, Sakaeda, T, Hirai, M & Matsui, T 2008, 'Pharmacokinetics-based optimal dose-exploration of mycophenolate mofetil in allogeneic hematopoietic stem cell transplantation', International journal of hematology, vol. 88, no. 1, pp. 104-110. https://doi.org/10.1007/s12185-008-0093-4

Pharmacokinetics-based optimal dose-exploration of mycophenolate mofetil in allogeneic hematopoietic stem cell transplantation. / Okamura, Atsuo; Yamamori, Motohiro; Shimoyama, Manabu; Kawano, Yuko; Kawano, Hiroki; Kawamori, Yuriko; Nishikawa, Shinichiro; Minagawa, Kentaro; Yakushijin, Kimikazu; Katayama, Yoshio; Sakaeda, Toshiyuki; Hirai, Midori; Matsui, Toshimitsu.

In: International journal of hematology, Vol. 88, No. 1, 01.07.2008, p. 104-110.

Research output: Contribution to journalArticle

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T1 - Pharmacokinetics-based optimal dose-exploration of mycophenolate mofetil in allogeneic hematopoietic stem cell transplantation

AU - Okamura, Atsuo

AU - Yamamori, Motohiro

AU - Shimoyama, Manabu

AU - Kawano, Yuko

AU - Kawano, Hiroki

AU - Kawamori, Yuriko

AU - Nishikawa, Shinichiro

AU - Minagawa, Kentaro

AU - Yakushijin, Kimikazu

AU - Katayama, Yoshio

AU - Sakaeda, Toshiyuki

AU - Hirai, Midori

AU - Matsui, Toshimitsu

PY - 2008/7/1

Y1 - 2008/7/1

N2 - 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.

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