Kishino S, Nomura A, Di Z S, Sugawara M, Iseki K, Kakinoki S, Kitabatake A, Miyazaki K
Department of Pharmacy, Hokkaido University Hospital, Hokkaido University, Sapporo, Japan.
Ther Drug Monit. 1995 Oct;17(5):449-53. doi: 10.1097/00007691-199510000-00003.
The elevation of alpha-1-acid glycoprotein (AAG) concentration and the binding characteristics of disopyramide (DP) to AAG in patients with renal insufficiency were investigated. The serum AAG concentration and protein binding of DP in patients were significantly greater than those in healthy subjects. However, in both the serum and the purified AAG, Scatchard analysis showed that the number of binding sites per molecule of AAG in patients was significantly lower than that in healthy subjects, although there was no difference in the dissociation constant (Kd). These results suggest that the AAG induced in renal insufficiency is qualitatively different from normal AAG. Moreover, the change of the unbound DP fraction when DP concentration was increased was larger in the patients than in the healthy controls. Therefore, monitoring of the unbound DP would be important for therapeutic drug monitoring in patients with renal insufficiency.
研究了肾功能不全患者α-1-酸性糖蛋白（AAG）浓度的升高以及丙吡胺（DP）与AAG的结合特性。患者血清中AAG浓度和DP的蛋白结合率显著高于健康受试者。然而，在血清和纯化的AAG中，Scatchard分析表明，尽管解离常数（Kd）没有差异，但患者每分子AAG的结合位点数显著低于健康受试者。这些结果表明，肾功能不全时诱导产生的AAG在性质上与正常AAG不同。此外，当DP浓度增加时，患者未结合DP分数的变化比健康对照者更大。因此，监测未结合的DP对于肾功能不全患者的治疗药物监测很重要。
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