Indinavir protein-free concentrations when used in indinavir/ritonavir combination therapy
Indinavir protein-free concentrations when used in indinavir/ritonavir combination therapy
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DOI：
10.1097/01.aids.0000174452.78497.54
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发表时间：
2005-07-01
期刊：
影响因子：
3.8
通讯作者：
Acosta, EP
中科院分区：
文献类型：
--
作者：
King, JR;John, JG;Acosta, EP
目的：描述利托那韦（RTV）存在时，茚地那韦（IDV）相对于IDV总血浆浓度的体内蛋白结合特性。设计：ACTG方案5055是一项多中心研究，比较每天两次剂量为800/200和400/400 mg的IDV/RTV在hiv感染成人中的安全性和药代动力学。方法：44例患者在治疗2周后进行12小时强化药代动力学评估。35例患者C-max给药后6和12小时的3份血浆样本用于测定未结合的IDV浓度。用超滤法分离血浆样品中的游离IDV，用紫外检测的高效液相色谱法测定。结果：在800/200和400/400组中，IDV蛋白结合分数在所有时间点上的平均值分别为53.4和51.8%。在800/200组中，C-max时的结合百分比为50%，而12 h时为56% （P = 0.008）。在400/400组中，C-max时的结合百分比为49%，而12 h时为54% （P = 0.008）。结论：本研究中IDV的血浆蛋白结合程度小于先前发表的单独使用IDV的数据。虽然各组间的IDV浓度不同，但800/200和400/400各组间所有时间点的IDV蛋白结合百分比没有差异。然而，与12 h相比，各组C-max时IDV蛋白结合的百分比显著降低，这可能表明IDV蛋白结合是浓度依赖性的。这些数据表明，RTV影响IDV蛋白结合特性，当RTV给药时，IDV也表现出浓度依赖性结合。(c) 2005年Lippincott Williams & Wilkins。
Objective: To describe the in vivo protein-binding characteristics of indinavir (IDV) in the presence of ritonavir (RTV) relative to total IDV plasma concentrations.Design: The ACTG protocol 5055 was a multicenter study comparing the safety and pharmacokinetics of IDV/RTV at doses of 800/200 and 400/400 mg twice daily in HIV-infected adults.Methods: Forty-four patients underwent a 12-h intensive pharmacokinetic assessment after 2 weeks of therapy. Three plasma samples from 35 patients at C-max 6 and 12 h post dose were used to determine the unbound IDV concentrations. Unbound IDV was separated in plasma samples using ultra-filtration and measured using high-performance liquid chromatography with UV detection.Results: Mean IDV protein-bound fraction across all time points in the 800/200 and 400/400 arm were 53.4 and 51.8%, respectively. In the 800/200 arm, percentage binding at C-max was 50% compared with 56% at 12 h (P = 0.008). In the 400/400 arm, percentage binding at C-max was 49% compared with 54% at 12 h (P = 0.008).Conclusions: The extent of plasma protein binding of IDV in this study was less than in previously published data with IDV alone. Although IDV concentrations differed across the arms, the percentage of IDV protein binding at all time points was not different between the 800/200 and 400/400 arms. However, the percentage of IDV protein binding at C-max was significantly lower compared with 12 h in each arm, possibly suggesting that IDV protein binding is concentration-dependent. These data suggest that RTV affects IDV protein-binding characteristics and IDV also exhibits concentration dependent binding when administered with RTV. (c) 2005 Lippincott Williams & Wilkins.