的贡献α1-acid糖蛋白lincosamides-plasma物种差异蛋白质绑定动力学。

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《下田儿子DS, Osabe M M, Kokue E

的贡献α1-acid糖蛋白lincosamides-plasma物种差异蛋白质绑定动力学。

J兽医杂志。1998年2月,21 (1):34-40。doi: 10.1046 / j.1365-2885.1998.00111.x。

PubMed ID
9507455 (在PubMed
]
文摘

蛋白结合动力学洁霉素(LM)和克林霉素(CM)使用等离子体,研究了白蛋白和α1-acid糖蛋白(AGP)来自人类、狗、牛和羊。根据罗森塔尔块LM和厘米,drug-binding财产等离子体特异性和非特异性结合,除了LM在羊、牛羊和厘米,只显示非特异性结合。离解常数(Kd)和绑定能力(Bmax)为特定的绑定和非特异性结合的比例常数(PC)如下:Kd = 3.14 mumol / L, Bmax = 15.28 mumol / L,电脑对人类= 0.19;Kd = 3.84 mumol / L, Bmax = 6.55 mumol / L PC为狗= 0.14;电脑为牛= 0.12;电脑为羊在LM和Kd = 0.94 = 0.16 mumol / L, Bmax = 12.24 mumol / L,电脑对人类= 4.98;Kd = 1.48 mumol / L, Bmax = 9.52 mumol / L PC为狗= 2.91;Kd = 1.22 mumol / L, Bmax = 4.45 mumol / L PC为牛= 2.40;PC的羊= 1.48厘米。每个物种的特定绑定不同,显示更多的差异Bmax而Kd。 The non-specific binding of LM was similar among species whereas that of CM was different, implying species difference. The drug-binding property of AGP for each species was all specific binding and the Kd was comparable to that obtained from plasma, indicating that AGP is a major specific binder in plasma. The lack of detection of specific binding for LM in cattle and sheep and for CM in sheep plasma could be attributable to a higher Kd and lower plasma AGP concentration compared with other species. The drug-binding property of albumin was characterized as all non-specific, without a great difference among species. Except for CM in sheep, the lower PC in albumin solution compared with that in plasma suggested the presence of another non-specific binder in plasma, i.e. lipoprotein. From the simulation of drug-binding percentage to AGP concentrations, AGP could be a major contributor to drug-plasma protein binding in pathological states. The degree of AGP-drug binding for each species could vary according to the degree of increase of AGP concentrations from a healthy to a pathological state, inducing a decrease in the unbound fraction (fp): 6.1 fold for dogs, 4.6 fold for humans, 1.8 fold for sheep and 1.4 fold for cattle in LM; 5.8 fold for dogs, 5.7 fold for cattle, 4.0 fold for humans and 1.5 fold for sheep in CM. Therefore, the disposition and efficacy of lincosamides affected by fp can be modified differently by the change of fp attributable to the alteration of plasma AGP concentration in each species.

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药物
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药物 航空公司 类 生物 药理作用 行动
洁霉素 Alpha-1-acid糖蛋白1 蛋白质 人类
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