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 › peer-review

9 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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10.1007/s13365-013-0172-z

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title = "Pharmacokinetic interactions of CEP-1347 and atazanavir in HIV-infected patients",

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.",

keywords = "Atazanavir, CEP-1347, Drug interactions, HIV, Mixed lineage kinases, Ritonavir",

author = "Qing Ma and Gelbard, {Harris A.} and Maggirwar, {Sanjay B.} and Stephen Dewhurst and Gendelman, {Howard E.} and Peterson, {Derick R.} and Robin Difrancesco and Hochreiter, {Jill S.} and Morse, {Gene D.} and Giovanni Schifitto",

year = "2013",

month = jun,

doi = "10.1007/s13365-013-0172-z",

language = "English (US)",

volume = "19",

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AU - Ma, Qing

AU - Gelbard, Harris A.

AU - Maggirwar, Sanjay B.

AU - Dewhurst, Stephen

AU - Gendelman, Howard E.

AU - Peterson, Derick R.

AU - Difrancesco, Robin

AU - Hochreiter, Jill S.

AU - Morse, Gene D.

AU - Schifitto, Giovanni

PY - 2013/6

Y1 - 2013/6

N2 - 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.

AB - 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.

KW - Atazanavir

KW - CEP-1347

KW - Drug interactions

KW - HIV

KW - Mixed lineage kinases

KW - Ritonavir

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

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