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两种强结合药物与人血清白蛋白结合参数计算的图形法与计算机化方法比较

Comparison of graphical and computerized methods for calculating binding parameters for two strongly bound drugs to human serum albumin.

作者信息

Vallner J J, Perrin J H, Wold S

出版信息

J Pharm Sci. 1976 Aug;65(8):1182-7. doi: 10.1002/jps.2600650813.

DOI:10.1002/jps.2600650813
PMID:62049
Abstract

The determination of drug-protein binding parameters (n's and K's) can lead to important information on the required therapeutic dosage regimen and possible clinical complications associated with competitive displacement of one drug by a concurrently administered agent. Graphical and computer estimates of the data are often incorrectly formulated, and and seldom are adequate data obtained at low binding ratios. Commonly used graphical procedures, inadequately formulated computer methods, and a statistically correct computer method were used to compare results obtained from a circular dichroic examination of dicumarol-human serum albumin and fenoprofen-human serum albumin interactions. Literature binding constants for dicumarol-albumin range from 1 X 10(5) to 30 times that figure, and it is shown here that a wide range in parameter estimates may be obtained depending on the method of data analysis. The parameter estimates in the case of fenoprofen-albumin are even more variable.

摘要

药物与蛋白质结合参数(n值和K值)的测定能够提供有关所需治疗剂量方案以及与同时给药的药物竞争性取代另一种药物相关的潜在临床并发症的重要信息。对数据的图形估计和计算机估计常常公式化错误,而且在低结合率情况下很少能获得足够的数据。使用常用的图形程序、公式化不当的计算机方法以及一种统计上正确的计算机方法来比较从双香豆素 - 人血清白蛋白和非诺洛芬 - 人血清白蛋白相互作用的圆二色性检查中获得的结果。双香豆素 - 白蛋白的文献结合常数范围为1×10⁵至该数值的30倍,并且在此表明,根据数据分析方法的不同,可能会获得参数估计值的广泛范围。非诺洛芬 - 白蛋白情况下的参数估计值变化更大。

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Eur J Drug Metab Pharmacokinet. 1984 Apr-Jun;9(2):109-16. doi: 10.1007/BF03189613.
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Determination of free fractions of tricyclic antidepressants.
Naunyn Schmiedebergs Arch Pharmacol. 1984 Sep;327(3):260-5. doi: 10.1007/BF00502459.
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Intraoperative ceforanide pharmacokinetics and protein binding.术中头孢雷特的药代动力学和蛋白结合情况。
Antimicrob Agents Chemother. 1985 Apr;27(4):487-90. doi: 10.1128/AAC.27.4.487.
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Conformation of dopamine at the dopamine receptor.多巴胺在多巴胺受体处的构象。
Proc Natl Acad Sci U S A. 1978 Jun;75(6):2641-3. doi: 10.1073/pnas.75.6.2641.