Influence of tenofovir, nevirapine and efavirenz on ritonavir-boosted atazanavir pharmacokinetics in HIV-infected patients
Influence of tenofovir, nevirapine and efavirenz on ritonavir-boosted atazanavir pharmacokinetics in HIV-infected patients
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DOI：
10.1007/s00228-006-0122-2
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发表时间：
2006-07-01
影响因子：
2.9
通讯作者：
Jolliet, Pascale
中科院分区：
文献类型：
--
作者：
Dailly, Eric;Tribut, Olivier;Jolliet, Pascale
目的：在 HIV（人类免疫缺陷病毒）感染患者中研究奈韦拉平、依非韦伦和替诺福韦联合给药对利托那韦增强的阿扎那韦药代动力学的影响。方法：在治疗药物监测的背景下进行群体药代动力学分析（87 名患者，121 个样本）。结果：与接受阿扎那韦/利托那韦和核苷逆转录酶抑制剂治疗的患者（A 组）相比，替诺福韦（B 组）、依非韦伦（C 组）或奈韦拉平（D 组）与阿扎那韦/利托那韦联合给药时，阿扎那韦清除率 (Cl/F) 显着增加：6.24 +/- 0.36 l h(-1)（A 组）对比 7.42 +/- 0.25 l h(-1)（B 组）对比 9.60 +/- 0.27 l h(-1)（C 组）对比 17.53 +/- 0.57 l h(-1)（D 组）（P < 0.001）。然而，阿扎那韦平均谷血浆浓度的降低仅在 D 组中显着：1.02 +/- 0.86 mg/l（A 组）对比 0.21 +/- 013 mg/l（D 组）（P < 0.001）。结论：阿扎那韦与奈韦拉平、依非韦伦和/或替诺福韦联合使用时清除率增加，提示在这种情况下应进行阿扎那韦的治疗药物监测。
Objective: The influence of nevirapine, efavirenz and tenofovir co-administration on ritonavir-boosted atazanavir pharmacokinetics was investigated in HIV (human immunodeficiency virus)-infected patients. Methods: A population pharmacokinetic analysis was performed in the context of therapeutic drug monitoring (87 patients, 121 samples). Results: A significant increase of atazanavir clearance (Cl/F) was found when either tenofovir (group B), efavirenz (group C), or nevirapine (group D) were co administered with atazanavir/ritonavir in comparison with patients treated with atazanavir/ritonavir and nucleoside reverse transcriptase inhibitors (group A): 6.24 +/- 0.36 l h(-1) (group A) versus 7.42 +/- 0.25 l h(-1) (group B) versus 9.60 +/- 0.27 l h(-1) (group C) versus 17.53 +/- 0.57 l h(-1) (group D) (P < 0.001). However, the decrease of the mean trough plasma concentration of atazanavir was significant only in group D: 1.02 +/- 0.86 mg/l (group A) versus 0.21 +/- 013 mg/l (group D) (P < 0.001). Conclusion: The increase in atazanavir clearance when it is used in combination with nevirapine, efavirenz and/or tenofovir suggests that therapeutic drug monitoring of atazanavir should be performed in such circumstances.