Kinetic studies of drug-protein interactions by using peak profiling and high-performance affinity chromatography: examination of multi-site interactions of drugs with human serum albumin columns.
Kinetic studies of drug-protein interactions by using peak profiling and high-performance affinity chromatography: examination of multi-site interactions of drugs with human serum albumin columns.
复制标题
通过使用峰值分析和高性能亲和力色谱法对药物蛋白相互作用的动力学研究：检查药物与人血清白蛋白柱的多位相互作用。
DOI：
10.1016/j.chroma.2010.10.070
复制
发表时间：
2011-04-15
期刊：
影响因子：
--
通讯作者：
Hage DS
中科院分区：
文献类型：
--
作者：
Tong Z;Schiel JE;Papastavros E;Ohnmacht CM;Smith QR;Hage DS
卡马西平和丙咪嗪是与人血清白蛋白(HSA)有显著结合的药物，人血清白蛋白是血液中含量最丰富的血清蛋白，也是体内许多药物的共同运输蛋白。关于这些药物与人血清白蛋白相互作用的动力学信息将对了解这些药物的药代动力学行为很有价值，并可能提供数据，从而改进生物样品中这些分析物的分析方法。用高效亲和层析法测定了卡马西平和丙咪嗪与人血清白蛋白的解离速率常数。该方法比较了每种药物和未保留物种在HSA色谱柱和对照色谱柱上的洗脱曲线。在这一过程中，考虑并比较了纠正这些药物与载体之间非特异性结合的各种方法。用该方法计算了人血清白蛋白与卡马西平和丙咪嗪相互作用的解离速率常数分别为1.70(±0.2)S~(-1)和0.67(±0.04)S~(-1)。这些结果与用其他方法或类似溶质与人血清白蛋白相互作用测得的速率常数符合得很好。本报告中描述的动力学研究方法不仅限于这些特定的药物或人血清白蛋白，还可以扩展到其他药物和蛋白质。
Carbamazepine and imipramine are drugs that have significant binding to human serum albumin (HSA), the most abundant serum protein in blood and a common transport protein for many drugs in the body. Information on the kinetics of these drug interactions with HSA would be valuable in understanding the pharmacokinetic behavior of these drugs and could provide data that might lead to the creation of improved assays for these analytes in biological samples. In this report, an approach based on peak profiling was used with high-performance affinity chromatography to measure the dissociation rate constants for carbamazepine and imipramine with HSA. This approach compared the elution profiles for each drug and a non-retained species on an HSA column and control column over a board range of flow rates. Various approaches for the corrections of non-specific binding between these drugs and the support were considered and compared in this process. Dissociation rate constants of 1.7 (± 0.2) s-1 and 0.67 (± 0.04) s-1 at pH 7.4 and 37 °C were estimated by this approach for HSA in its interactions with carbamazepine and imipramine, respectively. These results gave good agreement with rate constants that have determined by other methods or for similar solute interactions with HSA. The approach described in this report for kinetic studies is not limited to these particular drugs or HSA but can also be extended to other drugs and proteins.
登录
查看更多内容
影响因子：
4.1
作者：
Chattopadhyay, A;Hage, DS
通讯作者：
Hage, DS
影响因子：
3.6
作者：
RIETBROCK, N;LASSMANN, A
通讯作者：
LASSMANN, A
DOI：
10.1016/s0021-9673(01)87800-6
发表时间：
1984-01-01
期刊：
JOURNAL OF CHROMATOGRAPHY
影响因子：
--
作者：
MULLER, AJ;CARR, PW
通讯作者：
CARR, PW
影响因子：
2.9
作者：
Rich, RL;Day, YSN;Myszka, DG
通讯作者：
Myszka, DG
影响因子：
7.4
作者：
Talbert, AM;Tranter, GE;Francis, PL
通讯作者：
Francis, PL