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

doi:10.1007/s13365-013-0172-z

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 journal › Article

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 language	English (US)
Pages (from-to)	254-260
Number of pages	7
Journal	Journal of neurovirology
Volume	19
Issue number	3
DOIs	https://doi.org/10.1007/s13365-013-0172-z
State	Published - 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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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

Pharmacokinetic interactions of CEP-1347 and atazanavir in HIV-infected patients. / Ma, Qing; Gelbard, Harris A.; Maggirwar, Sanjay B.; Dewhurst, Stephen; Gendelman, Howard E.; Peterson, Derick R.; Difrancesco, Robin; Hochreiter, Jill S.; Morse, Gene D.; Schifitto, Giovanni.

In: Journal of neurovirology, Vol. 19, No. 3, 06.2013, p. 254-260.

Research output: Contribution to journal › Article

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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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