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

Q Ma, HA Gelbard, SB Maggirwar, S Dewhurst… - Journal of …, 2013 - Springer
Q Ma, HA Gelbard, SB Maggirwar, S Dewhurst, HE Gendelman, DR Peterson…
Journal of neurovirology, 2013Springer
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 …
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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