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Influence of H2-receptor antagonists and proton pump inhibitors on dasatinib pharmacokinetics in Japanese leukemia patients

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Abstract

Purpose

The objective of this study was to investigate the drug interaction between dasatinib and the gastric acid suppressants (H2-receptor antagonists (H2RA) famotidine and nizatidine and the proton pump inhibitor (PPI) lansoprazole in leukemia Japanese patients.

Methods

Eighteen patients treated with dasatinib and H2RA, PPI or no acid suppressant from whom were obtained a total of 34 pharmacokinetic profiles were enrolled in the study. Dasatinib plasma concentrations from samples obtained just prior to and 1, 2, and 4 h after oral dasatinib administration were analyzed by high-performance liquid chromatography.

Results

There were no significant correlations between the dose-adjusted total area under the observed plasma concentration–time curve (AUC0–4) of dasatinib and gender, age, weight, or body surface area. The only variable factor, the dasatinib dose-adjusted AUC0–4 for patients administered an H2RA or PPI, was significantly lower than for patients not administered an acid suppressant (median (quartile 1–quartile 3) values: 1.47 (0.79–2.29) versus 3.51 (2.50–5.45) ng h/mL/mg, respectively, P = 0.0008). Moreover, the plasma concentration 2 h (C2h) after dasatinib administration gave a high correlation with the AUC0–4 of dasatinib (r = 0.9419, P < 0.0001).

Conclusion

Clinicians should be aware that administration of an acid suppressant such as famotidine, nizatidine, and lansoprazole can decrease the absorption of dasatinib from the gastrointestinal tract, thereby resulting in a significant decrease in the plasma concentration of dasatinib. The combination of dasatinib and an acid suppressant requires careful therapeutic drug monitoring of the dasatinib plasma concentration to ensure effective patient exposure to the drug.

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Acknowledgments

This work was supported by a grant (no. 23590168) from the Japan Society for the Promotion of Science, Tokyo, Japan.

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Authors and Affiliations

  1. Department of Hematology, Nephrology, and Rheumatology, Akita University Graduate School of Medicine, Akita, Japan

    Naoto Takahashi & Kenichi Sawada

  2. Department of Pharmacy, Akita University Hospital, 1-1-1 Hondo, Akita, 010-8543, Japan

    Masatomo Miura & Takenori Niioka

Authors
  1. Naoto Takahashi
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  2. Masatomo Miura
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  3. Takenori Niioka
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  4. Kenichi Sawada
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Correspondence to Masatomo Miura.

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Takahashi, N., Miura, M., Niioka, T. et al. Influence of H2-receptor antagonists and proton pump inhibitors on dasatinib pharmacokinetics in Japanese leukemia patients. Cancer Chemother Pharmacol 69, 999–1004 (2012). https://doi.org/10.1007/s00280-011-1797-3

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  • DOI: https://doi.org/10.1007/s00280-011-1797-3

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