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Pharmacokinetics for once-daily modified release formulation of tacrolimus hydrate in unrelated hematopoietic stem cell transplantation

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Abstract

A once-daily modified release formulation of oral tacrolimus (Tac QD) has been developed in response to the problem of nonadherence. However, there have been no data available about the efficacy of Tac QD conversion from intravenous Tac (Tac i.v.) in allogeneic hematopoietic stem cell transplantation (allo-SCT). We analyzed the pharmacokinetics (PK) of Tac QD in allo-SCT recipients. A total of 10 patients with hematological malignancies who received allo-SCT from unrelated donors were enrolled. Patients received Tac i.v. at 0.03 mg/kg a day before transplantation. Administration of Tac i.v. was converted to Tac QD at a 1:4 ratio when the patients had recovered from regimen-related gastrointestinal toxicity and could tolerate oral medication. After conversion, six out of 10 patients (60 %) showed a sustained decrease in Tac exposure and required dose adjustment. The conversion from Tac i.v. to Tac QD should be performed under close medical supervision. Area under the curve (AUC) and the trough of Tac QD showed a correlation, and the trough should be maintained above 7.5 ng/ml to provide an adequate AUC. Although four patients received bone marrow from an HLA DRB1 1 antigen-mismatched unrelated donor, no patients developed grade III–IV acute graft-versus-host disease (GVHD). The modification of Tac QD to maintain a whole-blood trough concentration above 7.5 ng/ml may be as effective as Tac BID.

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Acknowledgments

This work was supported by Health and Labour Sciences Research Grants for Clinical Cancer Research from the Ministry of Health, Labour and Welfare, Japan. We thank the nursing staff who cared for the patients at Jikei University Hospital and SRL laboratory staff who analyzed the plasma concentration of Tac.

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Division of Clinical Oncology and Hematology, Jikei University School of Medicine, 3-25-8 Nishi Shinbashi, Minatoku, Tokyo, 105-8461, Japan

    Shingo Yano, Takeshi Saito, Hiroki Yokoyama, Tomohito Machishima, Takaki Shimada, Yuichi Yahagi, Katsuki Sugiyama, Yoji Ogasawara, Shinobu Takahara, Kinuyo Kasama, Atsushi Katsube, Yutaro Kamiyama, Kazuhito Suzuki, Yumiko Inui, Noriko Usui & Keisuke Aiba

  2. Department of Hematology and Oncology, St. Luke’s International Hospital, Tokyo, Japan

    Shinichiro Mori

  3. Department of Hematology and Hematopoietic Stem Cell Transplantation, National Cancer Center Hospital, Tokyo, Japan

    Takuya Yamashita

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  1. Shingo Yano
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  2. Shinichiro Mori
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  3. Takeshi Saito
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  14. Kazuhito Suzuki
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  15. Yumiko Inui
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  16. Noriko Usui
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  17. Keisuke Aiba
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  18. Takuya Yamashita
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Correspondence to Shingo Yano.

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Yano, S., Mori, S., Saito, T. et al. Pharmacokinetics for once-daily modified release formulation of tacrolimus hydrate in unrelated hematopoietic stem cell transplantation. Ann Hematol 94, 491–496 (2015). https://doi.org/10.1007/s00277-014-2233-7

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  • DOI: https://doi.org/10.1007/s00277-014-2233-7

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