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对人血清进行热处理以灭活HIV不会改变所选药物的蛋白质结合情况。

Heat treatment of human serum to inactivate HIV does not alter protein binding of selected drugs.

作者信息

Mosley A K, Brouwer K L

机构信息

School of Pharmacy, University of North Carolina, Chapel Hill 27599-7360, USA.

出版信息

Ther Drug Monit. 1997 Aug;19(4):477-9. doi: 10.1097/00007691-199708000-00019.

Abstract

Human immunodeficiency virus (HIV) may be transmitted via certain biological fluids, particularly blood. To minimize the risk of accidental exposure, the virus may be inactivated by heat treatment of blood, plasma, or serum samples at 54-56 degrees C for 5 h. The objective of this study was to determine whether heat treatment of human serum alters the protein binding of model compounds. Diazepam, phenytoin, and digitoxin were selected for investigation because they bind to three different sites on human serum albumin (HSA); propranolol also was examined since it binds to both HSA and alpha 1-acid glycoprotein. The unbound fraction of selected drugs was measured by ultrafiltration at 37 degrees C after addition of each compound to either untreated or heat-treated serum. The percentage unbound in serum for diazepam, phenytoin, digitoxin, and propranolol was not significantly different between the untreated and heat-treated samples. Therefore, heat treatment of serum does not appear to alter the binding characteristics at these four binding sites and would not be expected to lead to erroneous unbound concentration estimates and inappropriate adjustments in drug therapy.

摘要

人类免疫缺陷病毒(HIV)可通过某些生物体液传播,尤其是血液。为将意外暴露风险降至最低,可通过在54 - 56摄氏度对血液、血浆或血清样本进行5小时热处理来使病毒失活。本研究的目的是确定对人血清进行热处理是否会改变模型化合物的蛋白结合情况。选择地西泮、苯妥英和洋地黄毒苷进行研究,因为它们与人血清白蛋白(HSA)上的三个不同位点结合;还检测了普萘洛尔,因为它同时与人血清白蛋白和α1 - 酸性糖蛋白结合。在将每种化合物添加到未处理或热处理的血清中后,于37摄氏度通过超滤测量所选药物的游离分数。未处理和热处理样本中地西泮、苯妥英、洋地黄毒苷和普萘洛尔在血清中的游离百分比无显著差异。因此,血清热处理似乎不会改变这四个结合位点的结合特性,预计也不会导致游离浓度估计错误以及药物治疗中不适当的调整。

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