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Calcium carbonate does not affect imatinib pharmacokinetics in healthy volunteers

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Abstract

Purpose

Imatinib mesylate (Gleevec®/Glivec®) has revolutionized the treatment of chronic myeloid leukemias and gastrointestinal stromal tumors, and there is evidence for an exposure response relationship. Calcium carbonate is increasingly used as a calcium supplement and in the setting of gastric upset associated with imatinib therapy. Calcium carbonate could conceivably elevate gastric pH and complex imatinib, thereby influencing imatinib absorption and exposure. We aimed to evaluate whether use of calcium carbonate has a significant effect on imatinib pharmacokinetics.

Methods

Eleven healthy subjects were enrolled in a 2-period, open-label, single-institution, randomized crossover, fixed-schedule study. In one period, each subject received 400 mg of imatinib p.o. In the other period, 4,000 mg calcium carbonate (Tums Ultra®) was administered p.o. 15 min before 400 mg of imatinib. Plasma concentrations of imatinib and its active N-desmethyl metabolite CGP74588 were assayed by LC–MS; data were analyzed non-compartmentally and compared after log transformation.

Results

Calcium carbonate administration did not significantly affect the imatinib area under the plasma concentration versus time curve (AUC) (41.2 μg/mL h alone vs. 40.8 μg/mL h with calcium carbonate, P = 0.99), maximum plasma concentration (C max) (2.35 μg/mL alone vs. 2.39 μg/mL with calcium carbonate, P = 0.89).

Conclusions

Our results indicate that the use of calcium carbonate does not significantly affect imatinib pharmacokinetics.

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Acknowledgments

We thank the nursing staff of the University of Pittsburgh Cancer Institute Clinical Translational Research Center for their invaluable assistance. This work was supported by Novartis Pharmaceuticals Corporation (East Hanover, NJ, USA), NIH/NCRR/CTSA Grant UL1 RR024153. This project used the UPCI Clinical Pharmacology Analytical Facility (CPAF) and was supported in part by award P30CA047904.

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Authors and Affiliations

  1. Molecular Therapeutics/Drug Discovery Program, University of Pittsburgh Cancer Institute, Hillman Research Pavilion, Room G27E, 5117 Centre Avenue, Pittsburgh, PA, 15213-1863, USA

    Hussein Tawbi, Susan M. Christner, Edward Chu, James J. Lee, Shannon Puhalla, Ronald Stoller, Leonard R. Appleman & Jan H. Beumer

  2. Division of Hematology/Oncology, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, 15213, USA

    Hussein Tawbi, Edward Chu, James J. Lee, Shannon Puhalla, Ronald Stoller & Leonard R. Appleman

  3. Department of Biostatistics, University of Pittsburgh, Pittsburgh, PA, 15213, USA

    Yan Lin

  4. Clinical Research Services, University of Pittsburgh Cancer Institute, Pittsburgh, PA, 15213, USA

    Matthew Johnson, Emily T. Mowrey & Craig Cherrin

  5. Investigational Drug Service, UPMC Cancer Centers, Pittsburgh, PA, 15213, USA

    Brian M. Miller

  6. Department of Pharmaceutical Sciences, University of Pittsburgh School of Pharmacy, Pittsburgh, PA, 15213, USA

    Jan H. Beumer

Authors
  1. Hussein Tawbi
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  2. Susan M. Christner
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  3. Yan Lin
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  4. Matthew Johnson
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  5. Emily T. Mowrey
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  6. Craig Cherrin
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  7. Edward Chu
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  8. James J. Lee
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  9. Shannon Puhalla
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  10. Ronald Stoller
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  11. Leonard R. Appleman
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  12. Brian M. Miller
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  13. Jan H. Beumer
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Corresponding author

Correspondence to Jan H. Beumer.

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Tawbi, H., Christner, S.M., Lin, Y. et al. Calcium carbonate does not affect imatinib pharmacokinetics in healthy volunteers. Cancer Chemother Pharmacol 73, 207–211 (2014). https://doi.org/10.1007/s00280-013-2337-0

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  • DOI: https://doi.org/10.1007/s00280-013-2337-0

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