Estimation of serum-free 50-percent inhibitory concentrations for human immunodeficiency virus protease inhibitors lopinavir and ritonavir
Estimation of serum-free 50-percent inhibitory concentrations for human immunodeficiency virus protease inhibitors lopinavir and ritonavir
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DOI：
10.1128/aac.48.8.2911-2917.2004
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发表时间：
2004-08-01
影响因子：
4.9
通讯作者：
Kempf, DJ
中科院分区：
文献类型：
--
作者：
Hickman, D;Vasavanonda, S;Kempf, DJ
使用测定的游离分数和50%抑制浓度（IC 50）值的人免疫缺陷病毒蛋白酶抑制剂洛匹那韦（LPV）和利托那韦（RW）的组织培养基中的各种蛋白浓度范围从5至50%，我们估计了每种药物的无血清IC 50值。无血清IC 50值范围（LPV为0.64 - 0.77 ng/ml，RW为3.0 - 5.0 ng/ml）未显示出随蛋白浓度增加的趋势，尽管LPV的游离分数值差异为10倍（0.006 - 0.063），RTV的游离分数值差异为5倍（0.013 - 0.057）。MTT-MT4测定的平均无血清IC 50（LPV为0.69 ng/ml，RTV为4.0 ng/ml）可能是估计抑制商（IQ）的最准确参数，IQ是体内效力的相对测量值，定义为特定患者人群血浆中最小游离药物浓度（C-trough，C-free）与无血清IC 50 '的比值。使用这种方法，我们计算出LPV和RTV的蛋白酶激活剂初治患者的平均智商分别为67和5.6。
Using measured free fraction and 50% inhibitory concentration (IC50) values for the human immunodeficiency virus protease inhibitors lopinavir (LPV) and ritonavir (RW) in tissue culture media with various protein concentrations ranging from 5 to 50%, we estimated serum-free IC50 values for each drug. The range of serum-free IC50 values (0.64 to 0.77 ng/ml for LPV and 3.0 to 5.0 ng/ml for RW) did not exhibit a trend with increasing protein concentrations, despite a 10-fold difference in the free fraction value (0.006 to 0.063) for LPV and a 5-fold difference in the free fraction value (0.013 to 0.057) for RTV. The mean serum-free IC50 by the MTT-MT4 assay (0.69 ng/ml for LPV and 4.0 ng/ml for RTV) may be the most accurate parameter for the estimation of the inhibitory quotient (IQ), a relative measure of in vivo potency defined as the ratio of the minimal free drug concentration in plasma (C-trough,C-free) for a specific patient population and the serum-free IC50'. Using this approach, we calculated the average IQs for protease inhibitor-naive patients for LPV and RTV to be 67 and 5.6, respectively.