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(½) 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.
authors.affiliation: Center for Human Experimental Therapeutics, Clinical and Translational Sciences Institute, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA.
authors.forename: Qing
authors.initials: Q
authors.lastname: Ma
authors.forename: Harris A
authors.initials: HA
authors.lastname: Gelbard
authors.forename: Sanjay B
authors.initials: SB
authors.lastname: Maggirwar
authors.forename: Stephen
authors.initials: S
authors.lastname: Dewhurst
authors.forename: Howard E
authors.initials: HE
authors.lastname: Gendelman
authors.forename: Derick R
authors.initials: DR
authors.lastname: Peterson
authors.forename: Robin
authors.initials: R
authors.lastname: DiFrancesco
authors.forename: Jill S
authors.initials: JS
authors.lastname: Hochreiter
authors.forename: Gene D
authors.initials: GD
authors.lastname: Morse
authors.forename: Giovanni
authors.initials: G
authors.lastname: Schifitto
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D000069446:Atazanavir Sulfate; D018791:CD4 Lymphocyte Count; D002227:Carbazoles / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D004334:Drug Administration Schedule; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1 / Q000187:drug effects / Q000254:growth & development; D006207:Half-Life; D006801:Humans; D020930:MAP Kinase Kinase Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D018697:Nootropic Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D009842:Oligopeptides / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D011725:Pyridines / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D019438:Ritonavir / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*
chemical_list: D019380:Anti-HIV Agents; D002227:Carbazoles; D018697:Nootropic Agents; D009842:Oligopeptides; D047428:Protein Kinase Inhibitors; D011725:Pyridines; C106592:3,9-bis((ethylthio)methyl)-K-252a; D000069446:Atazanavir Sulfate; D020930:MAP Kinase Kinase Kinases; D019438:Ritonavir