Journal of NeuroVirology

, Volume 19, Issue 3, pp 254–260

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

  • Qing Ma
  • Harris A. Gelbard
  • Sanjay B. Maggirwar
  • Stephen Dewhurst
  • Howard E. Gendelman
  • Derick R. Peterson
  • Robin DiFrancesco
  • Jill S. Hochreiter
  • Gene D. Morse
  • Giovanni Schifitto
Article

DOI: 10.1007/s13365-013-0172-z

Cite this article as:
Ma, Q., Gelbard, H.A., Maggirwar, S.B. et al. J. Neurovirol. (2013) 19: 254. doi:10.1007/s13365-013-0172-z

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 T1/2 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.

Keywords

CEP-1347 Atazanavir Ritonavir HIV Drug interactions Mixed lineage kinases 

Copyright information

© Journal of NeuroVirology, Inc. 2013

Authors and Affiliations

  • Qing Ma
    • 8
    • 11
    • 12
  • Harris A. Gelbard
    • 1
    • 5
    • 6
  • Sanjay B. Maggirwar
    • 5
  • Stephen Dewhurst
    • 5
  • Howard E. Gendelman
    • 9
    • 10
  • Derick R. Peterson
    • 4
  • Robin DiFrancesco
    • 11
  • Jill S. Hochreiter
    • 11
  • Gene D. Morse
    • 3
    • 8
    • 11
    • 12
  • Giovanni Schifitto
    • 1
    • 2
    • 7
    • 13
  1. 1.Department of NeurologyUniversity of Rochester School of Medicine and DentistryRochesterUSA
  2. 2.Department of Imaging SciencesUniversity of Rochester School of Medicine and DentistryRochesterUSA
  3. 3.Department of Pharmacology and PhysiologyUniversity of Rochester School of Medicine and DentistryRochesterUSA
  4. 4.Department of Biostatistics and Computational BiologyUniversity of Rochester School of Medicine and DentistryRochesterUSA
  5. 5.Department of Microbiology and ImmunologyUniversity of Rochester School of Medicine and DentistryRochesterUSA
  6. 6.Center for Neural Development and DiseaseUniversity of Rochester School of Medicine and DentistryRochesterUSA
  7. 7.Clinical Research CenterUniversity of Rochester School of Medicine and DentistryRochesterUSA
  8. 8.Center for Human Experimental Therapeutics, Clinical and Translational Sciences InstituteUniversity of Rochester School of Medicine and DentistryRochesterUSA
  9. 9.Department of Pharmacology and Experimental NeuroscienceUniversity of Nebraska Medical CenterOmahaUSA
  10. 10.Department of Internal MedicineUniversity of Nebraska Medical CenterOmahaUSA
  11. 11.Translational Pharmacology Research CoreNew York State Center of Excellence in Bioinformatics and Life SciencesBuffaloUSA
  12. 12.Department of Pharmacy Practice, School of Pharmacy and Pharmaceutical SciencesUniversity at BuffaloBuffaloUSA
  13. 13.Department of Neurology, Movement and Inherited Neurologic DisordersClinical Trials Coordination CenterRochesterUSA

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