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Pharmacokinetic interactions of CEP-1347 and atazanavir in HIV-infected patients

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Abstract

CEP-1347 is a potent inhibitor of mixed lineage kinase (MLK), which was investigated for ameliorating HIV-associated neurocognitive disorders. CEP-1347 and atazanavir pharmacokinetics were determined when CEP-1347 50 mg twice daily was administered to HIV-infected patients (n = 20) receiving combination antiretroviral therapy including atazanavir and ritonavir (ATV/RTV, 300/100 mg) once daily continuously. Co-administration of CEP-1347 and ATV/RTV resulted with significant changes in pharmacokinetics of ATV but not RTV. Specifically, an increase in ATV accumulation ratio of 15 % (p = 0.007) and a prolongation of T 1/2 from 12.7 to 15.9 h (p = 0.002) were observed. The results suggested that co-administration of CEP-1347 with ATV/RTV in HIV-infected patients might result in limited impact on ATV but not on RTV pharmacokinetics.

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Acknowledgments

The dedication of the clinical research staff of the Center for Human Experimental Therapeutics and the Clinical and Translational Science Institute at University of Rochester, and the Translational Pharmacology Research Core at the New York State Center of Excellence in Bioinformatics and Life Sciences, University at Buffalo, is appreciated. This project was supported in part by grant P01MH064570 from the National Institute of Mental Health. Dr. Qing Ma is currently supported by grant K08MH098794.

Conflict of interest

The authors declared no conflict of interest.

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Authors and Affiliations

  1. Department of Neurology, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA

    Harris A. Gelbard & Giovanni Schifitto

  2. Department of Imaging Sciences, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA

    Giovanni Schifitto

  3. Department of Pharmacology and Physiology, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA

    Gene D. Morse

  4. Department of Biostatistics and Computational Biology, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA

    Derick R. Peterson

  5. Department of Microbiology and Immunology, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA

    Harris A. Gelbard, Sanjay B. Maggirwar & Stephen Dewhurst

  6. Center for Neural Development and Disease, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA

    Harris A. Gelbard

  7. Clinical Research Center, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA

    Giovanni Schifitto

  8. Center for Human Experimental Therapeutics, Clinical and Translational Sciences Institute, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA

    Qing Ma & Gene D. Morse

  9. Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE, USA

    Howard E. Gendelman

  10. Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE, USA

    Howard E. Gendelman

  11. Translational Pharmacology Research Core, New York State Center of Excellence in Bioinformatics and Life Sciences, Buffalo, NY, USA

    Qing Ma, Robin DiFrancesco, Jill S. Hochreiter & Gene D. Morse

  12. Department of Pharmacy Practice, School of Pharmacy and Pharmaceutical Sciences, University at Buffalo, Buffalo, NY, USA

    Qing Ma & Gene D. Morse

  13. Department of Neurology, Movement and Inherited Neurologic Disorders, Clinical Trials Coordination Center, 1351 Mount Hope Avenue, Suite 223, Rochester, NY, 14620, USA

    Giovanni Schifitto

Authors
  1. Qing Ma
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  2. Harris A. Gelbard
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  3. Sanjay B. Maggirwar
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  4. Stephen Dewhurst
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  5. Howard E. Gendelman
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  6. Derick R. Peterson
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  7. Robin DiFrancesco
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  8. Jill S. Hochreiter
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  9. Gene D. Morse
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  10. Giovanni Schifitto
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Correspondence to Giovanni Schifitto.

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Ma, Q., Gelbard, H.A., Maggirwar, S.B. et al. Pharmacokinetic interactions of CEP-1347 and atazanavir in HIV-infected patients. J. Neurovirol. 19, 254–260 (2013). https://doi.org/10.1007/s13365-013-0172-z

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  • DOI: https://doi.org/10.1007/s13365-013-0172-z

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