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

Research output: Contribution to journalArticle

8 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)254-260
Number of pages7
JournalJournal of neurovirology
Volume19
Issue number3
DOIs
StatePublished - Jun 2013

Keywords

  • Atazanavir
  • CEP-1347
  • Drug interactions
  • HIV
  • Mixed lineage kinases
  • Ritonavir

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology
  • Cellular and Molecular Neuroscience
  • Virology

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  • Cite this

    Ma, Q., Gelbard, H. A., Maggirwar, S. B., Dewhurst, S., Gendelman, H. E., Peterson, D. R., Difrancesco, R., Hochreiter, J. S., Morse, G. D., & Schifitto, G. (2013). Pharmacokinetic interactions of CEP-1347 and atazanavir in HIV-infected patients. Journal of neurovirology, 19(3), 254-260. https://doi.org/10.1007/s13365-013-0172-z