Pharmacokinetic interactions of CEP-1347 and atazanavir in HIV-infected patients
Pharmacokinetic interactions of CEP-1347 and atazanavir in HIV-infected patients
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DOI：
10.1007/s13365-013-0172-z
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发表时间：
2013-06-01
影响因子：
3.2
通讯作者：
Schifitto, Giovanni
中科院分区：
文献类型：
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作者：
Ma, Qing;Gelbard, Harris A.;Schifitto, Giovanni
CEP-1347是混合谱系激酶（MLK）的有效抑制剂，其被研究用于改善HIV相关的神经认知障碍。当CEP-1347 50 mg每日两次给予接受阿扎那韦和利托那韦（ATV/RTV，300/100 mg）每日一次连续抗逆转录病毒治疗的HIV感染患者（n = 20）时，测定CEP-1347和阿扎那韦的药代动力学。CEP-1347和ATV/RTV联合给药导致ATV而非RTV的药代动力学发生显著变化。具体而言，观察到ATV蓄积率增加15%（p = 0.007），T（1/2）从12.7 h延长至15.9 h（p = 0.002）。结果表明，CEP-1347与ATV/RTV在HIV感染患者中联合给药可能对ATV产生有限影响，但对RTV药代动力学影响不大。
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.