健康受试者和肾病患者中丙戊酸的血浆蛋白结合情况。
Plasma protein binding of valproic acid in healthy subjects and in patients with renal disease.
作者信息
Gugler R, Mueller G
出版信息
Br J Clin Pharmacol. 1978 May;5(5):441-6. doi: 10.1111/j.1365-2125.1978.tb01652.x.
Abstract
1 Based on the Scatchard plot of the binding data of valproic acid (VPA) it is concluded that the drug is bound by two groups of binding sites with the association constants K1=40.0 X 10(-3) and K2=0.39 X 10(3), and the number of binding sites n1=1.5 and n2=6.8. 2 The binding is dependent on dialysis time, on temperature, on the drug concentration, and on the protein concentration in plasma. 3 At therapeutic plasma concentrations unbound VPA is 8.4 +/- 2.5%, but is increased to 20.3 +/- 4.7% in patients with significant impairment of renal function (P less than 0.001). 4 In patients with renal disease a good correlation is found between unbound VPA and serum creatinine, creatinine clearance, blood nitrogen and uric acid, respectively. A poor correlation is seen between unbound VPA and total protein or albumin concentration in plasma.
摘要
1 根据丙戊酸（VPA）结合数据的Scatchard图得出结论，该药物由两组结合位点结合，缔合常数K1 = 40.0×10⁻³和K2 = 0.39×10³，结合位点数n1 = 1.5和n2 = 6.8。2 这种结合取决于透析时间、温度、药物浓度以及血浆中的蛋白质浓度。3 在治疗性血浆浓度下，未结合的VPA为8.4±2.5%，但在肾功能严重受损的患者中增加至20.3±4.7%（P小于0.001）。4 在肾病患者中，未结合的VPA分别与血清肌酐、肌酐清除率、血氮和尿酸之间存在良好的相关性。未结合的VPA与血浆中的总蛋白或白蛋白浓度之间的相关性较差。
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