University of Colorado Denver, Aurora, USA.
AIDS. 2011 Jul 31;25(12):1489-96. doi: 10.1097/QAD.0b013e328348fc41.
To describe the pharmacokinetics of atazanavir (ATV) and ritonavir-boosted ATV (ATV/r) in children aged 91 days to 21 years.
A phase I/II, open-label, multicenter study of once-daily ATV and ATV/r as part of combination antiretroviral treatment in HIV-infected treatment-experienced and treatment-naive children.
Sites in the United States and South Africa.
One hundred and ninety-five children enrolled; 172 had evaluable ATV pharmacokinetics on day 7.
Children were entered in age, dose, and formulation (powder or capsule) cohorts. Intensive pharmacokinetic sampling occurred 7 days after starting ATV. ATV doses were increased or decreased if the 24-h area under the concentration time curves (AUC0-24hr) were less than 30 or more than 90 μg × h/ml, respectively.
Cohorts satisfied protocol-defined pharmacokinetic criteria if the median ATV AUC0-24hr was 60 μg × h/ml or less, and AUC0-24hr and ATV concentrations 24-h postdose (C24) were more than 30 μg × h/ml and at least 60 ng/ml, respectively, in at least 80% of the children, with no individual AUC0-24hr less than 15 μg × h/ml.
Unboosted ATV capsules satisfied pharmacokinetic criteria at a dose of 520 mg/m for those aged more than 2 to 13 years or less and 620 mg/m for those aged more than 13 to 21 years or less. ATV/r capsules satisfied criteria at a dose of 205 mg/m for those aged more than 2 to 21 years or less. ATV/r powder satisfied criteria at a dose of 310 mg/m for those aged more than 2 to 13 years or less, but pharmacokinetics in those aged 2 years or less were highly variable.
Body surface area-determined doses of ATV capsules and of ATV/r powder and capsules provide ATV exposures in children of more than 2 years that approximate concentrations in adults receiving ATV/r.
描述 91 天至 21 岁儿童中阿扎那韦（ATV）和利托那韦增强的阿扎那韦（ATV/r）的药代动力学。
一项 I/II 期、开放性、多中心研究，评估了作为 HIV 感染的经验治疗和初治儿童联合抗逆转录病毒治疗的一部分的每日一次 ATV 和 ATV/r。
美国和南非的多个地点。
195 名儿童入组；172 名儿童在第 7 天有可评估的 ATV 药代动力学数据。
儿童按年龄、剂量和制剂（粉末或胶囊）分组。在开始服用 ATV 后 7 天进行强化药代动力学采样。如果 24 小时 AUC0-24hr 小于 30 或大于 90μg×h/ml，则分别增加或减少 ATV 剂量。
如果中位数 ATV AUC0-24hr 小于等于 60μg×h/ml，并且 AUC0-24hr 和 ATV 浓度 24 小时后（C24）分别大于 30μg×h/ml 和至少 60ng/ml，且至少 80%的儿童中有 80%以上的个体 AUC0-24hr 大于 15μg×h/ml，则符合方案定义的药代动力学标准。
未增强的 ATV 胶囊在年龄大于 2 至 13 岁或以下的儿童中剂量为 520mg/m，年龄大于 13 至 21 岁或以下的儿童中剂量为 620mg/m 时，满足药代动力学标准。ATV/r 胶囊在年龄大于 2 至 21 岁或以下的儿童中剂量为 205mg/m 时，满足标准。ATV/r 粉末在年龄大于 2 至 13 岁或以下的儿童中剂量为 310mg/m 时满足标准，但 2 岁或以下儿童的药代动力学变化很大。
根据体表面积确定的 ATV 胶囊和 ATV/r 粉末和胶囊剂量，为 2 岁以上儿童提供了接近接受 ATV/r 治疗的成人的 ATV 暴露量。
