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Different effects of lansoprazole and rabeprazole on the plasma voriconazole trough levels in allogeneic hematopoietic cell transplant recipients

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Abstract

Voriconazole (VRC) is widely used as prophylaxis and in the treatment of invasive fungal disease (IFD) after allogeneic hematopoietic cell transplantation (HCT). We retrospectively examined the results of VRC therapeutic drug monitoring (TDM) in allogeneic HCT recipients. A total of 474 samples were obtained from 59 adult patients who received VRC during the first 100 days following HCT between 2009 and 2014 in our institute. Seventeen patients received VRC for prophylaxis of IFD, and 42 received VRC for the empirical or preemptive therapy for IFD. A total of 299 samples (63 %) were obtained during the administration of the intravenous form of VRC. The median VRC daily dose based on the actual body weight was 6.68 mg/kg/day (range, 1.92–10.41 mg/kg/day). The median VRC trough level was 0.99 mg/l (range, <0.09–5.45 mg/l). The multivariate analysis using a logistic regression model demonstrated significantly higher VRC trough levels (≥1.0 mg/l) in males (P < 0.001), empirical or preemptive therapy (P = 0.002), VRC daily dose based on the actual body weight ≥7 mg/kg/day (P < 0.001), and concomitant use of lansoprazole as compared to rabeprazole (P < 0.001). The concomitant use of calcineurin inhibitors and corticosteroids had no effects on VRC trough levels in multivariate analysis. These data suggest that lansoprazole and rabeprazole have different effects on the plasma VRC trough levels in the allogeneic HCT recipients.

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Acknowledgments

The authors thank all of the physicians and staff at the hospital in this study. A.T. received research grants from pfizer. The other authors declare no competing financial interests.

Author contributors

T.Y. and T.K. designed the research, analyzed data, and wrote the manuscript; T.K., S.K., S.T., and A.T. performed transplantation; and all authors contributed to write the paper.

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    Authors and Affiliations

    1. Department of Pharmacy, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan

      Takeo Yasu & Yosuke Kurokawa

    2. Department of Hematology/Oncology, The Institute of Medical Science, The University of Tokyo, 4-6-1, Shirokanedai, Minato-ku, Tokyo, 108-8639, Japan

      Takaaki Konuma, Seiko Kato, Satoshi Takahashi & Arinobu Tojo

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    1. Takeo Yasu
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    2. Takaaki Konuma
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    Correspondence to Takaaki Konuma.

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    The institutional review board of the Institute of Medical Science, The University of Tokyo, has approved this retrospective study.

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    Takeo Yasu and Takaaki Konuma contributed equally to this work.

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    Yasu, T., Konuma, T., Kato, S. et al. Different effects of lansoprazole and rabeprazole on the plasma voriconazole trough levels in allogeneic hematopoietic cell transplant recipients. Ann Hematol 95, 1845–1851 (2016). https://doi.org/10.1007/s00277-016-2782-z

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