在 HIV 感染患者中 CEP-1347 与阿扎那韦的药代动力学相互作用。
Pharmacokinetic interactions of CEP-1347 and atazanavir in HIV-infected patients.
机构信息
Center for Human Experimental Therapeutics, Clinical and Translational Sciences Institute, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA.
出版信息
J Neurovirol. 2013 Jun;19(3):254-60. doi: 10.1007/s13365-013-0172-z. Epub 2013 Jun 5.
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.
摘要
CEP-1347 是一种混合谱系激酶（MLK）的有效抑制剂，用于改善 HIV 相关神经认知障碍。当 CEP-1347 50mg 每日两次与每日一次的含ritonavir 的 atazanavir（ATV/RTV，300/100mg）联合用于接受抗逆转录病毒治疗的 HIV 感染患者（n=20）时，测定了 CEP-1347 和 atazanavir 的药代动力学。CEP-1347 与 ATV/RTV 联合使用导致 ATV 的药代动力学发生显著变化，但 RTV 无变化。具体而言，观察到 ATV 蓄积率增加 15%（p=0.007）和 T(½)从 12.7 小时延长至 15.9 小时（p=0.002）。结果表明，在 HIV 感染患者中，CEP-1347 与 ATV/RTV 联合使用可能对 ATV 的影响有限，但对 RTV 的药代动力学无影响。
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